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Results for “Mucositis”

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At least 19 recordsLinked to original sources

PubMed1993

Induction of mucosal disease in cattle persistently infected with noncytopathic bovine viral diarrhea-mucosal disease virus by superinfection with cytopathic bovine viral diarrhea-mucosal disease virus.

Three head of cattle persistently infected with noncytopathic bovine viral diarrhea-mucosal disease virus (ncBVD-MDV) were superinfected naturally or experimentally with cytopathic bovine viral diarrhea-mucosal disease virus (cBVD-MDV). In the naturally superinfected case, one animal manifested pyrexia and severe diarrhea, and died without developing antibodies to cBVD-MDV. However, another animal survived with only continual slight anorexia and pyrexia, and developed strong resistance to the superinfected strain. In the experimental cases, induction of MD was unsuccessful in two persistently infected cattle when superinfected with cBVD-MDV antigenically heterologous for persistently infected ncBVD-MDV. They also developed antibodies to the cBVD-MDV strain with which they had been infected. After 6 months, these cattle were infected again with a cBVD-MDV strain different from that used in the previous experiment. One animal infected with this strain, which was antigenically homologous to the persistently infected strain, died after developing MD symptoms without developing antibodies to the infecting strain. It is suggested that the antigenic relationship between the persistent ncBVD-MDV and the superinfected cBVD-MDV was an important factor in developing MD.

Animals↗

PubMed1999

Mucosal immunity and inflammation. III. The mucosal antigen barrier: cross talk with mucosal cytokines.

We have known for many years that mucosal responses to antigens are regulated by immune cells and their molecular signals. More recently, it has become clear that epithelial cells also synthesize and secrete chemokines and cytokines. A sophisticated system of bidirectional cytokine signals is responsible for immune activation in the case of enteropathogens vs. immune suppression to food and commensal microbial antigens. A key factor in determining antigen handling is the route taken by antigens across the epithelial barrier. Cytokines and other mucosal messenger molecules play a critical role in the regulation of transepithelial antigen transport.

Animals↗

PubMed2000

Prevention of oral mucositis or oral candidiasis for patients with cancer receiving chemotherapy (excluding head and neck cancer).

BACKGROUND: Treatment of cancer with chemotherapy is becoming increasingly more effective but is associated with short and long-term side effects. Oral side effects remain a major source of illness despite the use of a variety of agents to prevent them. OBJECTIVES: To evaluate the effectiveness of oral (and topical) prophylactic agents for oral mucositis and oral candidiasis in patients with cancer (excluding head and neck cancer), compared with placebo or no treatment. SEARCH STRATEGY: Computerised MEDLINE, EMBASE, CINAHL, CANCERLIT, the Cochrane Controlled Trials Register and the Cochrane Oral Health Group Specialist Register search up to July 1999. Reference lists from relevant articles were scanned and the authors of eligible studies were contacted to identify trials and obtain additional information. SELECTION CRITERIA: Studies were selected if they met the following criteria: design - random or quasi-random allocation of participants; participants - anyone with cancer receiving chemotherapy (excluding head and neck cancer); interventions - prophylactic agents prescribed to reduce oral conditions arising from cancer or its treatment; outcomes - mucositis and oral candidiasis. DATA COLLECTION AND ANALYSIS: Information regarding methods, participants, interventions and outcome measures and results were independently extracted, in duplicate, by two reviewers (JC & HW). Specialist advice was sought to categorise interventions. Authors were contacted for details of randomisation and withdrawals and a quality assessment was carried out using the Jadad criteria (Jadad 1998). The Cochrane Oral Health Group statistical guidelines were followed and relative risk values calculated using random effects models where significant heterogeneity was detected (P < 0.1). MAIN RESULTS: Thirty-eight reports of trials were initially included. Two were duplicate reports and nine were excluded as there was no useable information. Of the 27 useable studies 14 had data for mucositis comprising 945 randomised patients and 15 included data for oral candidiasis with 1164 randomised patients. Of the eight prophylactic agents used for mucositis only one, ice chips, was effective (Relative risk 0.57, 95% CI 0.43 to 0.77, chi-square for heterogeneity = 0.26 (df = 1), p = 0.61). The NNT to prevent one extra case of mucositis over the baseline incidence using ice chips was 4 (95%CI: 3 to 7). The NNT for when the baseline incidence of mucositis in the population ranges from 50% to 80% are 5 to 4 respectively. There is evidence that antifungal agents which are partially or fully absorbed from the gastrointestinal tract prevent oral candidiasis and that the partially absorbed agents may be more effective than the fully absorbed agents. The RR for partially absorbed agents was 0.13 (95% CI 0.06 to 0.27, chi-square for heterogeneity = 5.3 (df = 3), P = 0. 15). The NNT to prevent one extra case of oral candidiasis over the baseline incidence using partially absorbed drugs was 3 (95% CI: 3 to 5). The NNT for when the baseline incidence of oral candidiasis in the population ranges from 30% to 70% are 4 to 2 respectively. The general reporting of RCT's was poor however the median Jadad score was acceptable and improved further when the authors provided additional information. The sensitivity analysis confirmed the findings for oral candidiasis. REVIEWER'S CONCLUSIONS: There is some evidence that ice chips prevent mucositis. None of the other prophylactic agents included in this review prevented mucositis. There is evidence that prophylactic use of antifungal agents which are absorbed or partially absorbed from the gastrointestinal tract reduce the clinical signs of oral candidiasis, and the partially absorbed drugs may be more effective. Future trials in this area should address the link between oral and general health including outcomes relevant to the patient. Collaboration between medical and dental teams is indicated.

Administration, Oral↗

PubMed1998

Mucosal responses to parenteral and mucosal vaccines.

Most human pathogens are acquired through mucosal portals of entry, and replicate in the mucosal tissues. Subsequently, the infecting agent may invade the blood stream and produce disease at distant systemic sites. However, a large number of pathogenic organisms are limited to development of disease only at the site of initial mucosal replication. Studies carried out with naturally acquired infections and mucosally delivered vaccines have provided strong evidence for the existence of a common mucosal immune system in the organized lymphoid follicles in respiratory and intestinal epithelium, and in the mucosa of genital tract, mammary glands, conjunctiva, upper airways, and the middle ear cavity. Mucosal application of live attenuated oral poliovaccine (OPV), rubella virus vaccine (RA 27/3), adenoviruses, influenza A virus, rotavirus, salmonella, and cholera vaccines have demonstrated consistent development of secretory IgA, serum antibody, and cellular immune responses. Mucosal immunization appears to result in preferential expression of several integrins and cell adhesion molecules associated with homing of lymphocytes to mucosal sites of immunization. Induction of mucosal immune responses often result in specific protection against reinfection challenge and against illness. Replicating agents introduced via the parenteral route also result in the development of mucosal responses and protection against systemic illness. Parenteral immunization with non-replicating agents often fails to induce specific mucosal responses. Such immunization, however, is quite effective in mounting high levels of serum antibody with development of protection against systemic illness. Parenteral vaccines, such as enhanced potency inactivated polio vaccine (eIPV), Haemophilus influenzae type B (HIB), hepatitis B virus (HBV), and other non-mucosal vaccines, have been highly effective in preventing systemic disease during subsequent exposure to natural infection. Recent evidence has shown that parenteral immunization can also be quite effective in inducing varying degrees of functional mucosal antibody responses as detected by ELISA and less frequently by neutralization. Systemic illnesses such as poliomyelitis and Haemophilus influenzae meningitis and community circulation of these agents has been eliminated or significantly limited in many parts of the world with the exclusive use of inactivated vaccines. Based on these observations, it is suggested that development of serum immunological responses are effective in the prevention of systemic disease regardless of the types of vaccines or route of their administration. However, induction of pathogen-specific antibody or cellular immunity at the mucosal sites is best elicited by mucosal application of the antigen.

Antibodies, Viral↗

PubMed1990

Mucosal blood flow stasis and hypoxemia as the pathogenesis of acute gastric mucosal injury: role of endogenous leukotrienes and prostaglandins.

To clarify the roles of endogenous leukotrienes and prostaglandins in the ethanol-induced gastric mucosal injury, the effect of AA-861 (a selective 5-lipoxygenase inhibitor) and indomethacin (a cyclooxygenase inhibitor) on the ethanol-induced gastric mucosal lesions was investigated in fasted rats. Furthermore, the effect of these agents on the gastric mucosal microcirculatory disturbance induced by ethanol was also investigated using laser Doppler velocimetry and reflectance spectrophotometry. Forty percent ethanol caused mucosal microcirculatory stasis and mucosal hypoxemia, followed by mucosal injury. The pretreatment with AA-861 reduced the mucosal injury and significantly reduced the mucosal congestion and hypoxia induced by 40% ethanol. The pretreatment with indomethacin did not reduce the gastric mucosal damage or influence the mucosal blood flow stasis and the mucosal hypoxemia induced by ethanol. These results suggested that the increase of endogenous leukotrienes after intragastric administration of ethanol is responsible for the mucosal microcirculatory disturbance and mucosal tissue hypoxemia resulting in the mucosal injury, and that the decrease of prostaglandins alone may not play an important role in ethanol-induced mucosal injury.

Animals↗

PubMed2005

A critical role of gastric mucosal ascorbic acid in the progression of acute gastric mucosal lesions induced by compound 48/80 in rats.

AIM: To study the role of gastric mucosal ascorbic acid (AA) in the progression of acute gastric mucosal lesions induced by compound 48/80 (C48/80), a mast cell degranulator, in rats. METHODS: C48/80 (0.75 mg/kg) was intraperitoneally injected to fasted Wistar rats. Oral administration of AA (10, 50 or 100 mg/kg) was performed 0.5 h after C48/80 treatment. Determinations for gastric mucosal lesion severity and blood flow, and assays for gastric mucosal total AA, reduced AA, oxidized AA, vitamin E, thiobarbituric acid reactive substances (TBARS), adherent mucus, nitrite/nitrate (NOx), non-protein SH (NPSH), and myeloperoxidase (MPO), and serum total AA, reduced AA, oxidized AA, and NOx were conducted 0.5 and 3 h after C48/80 treatment. RESULTS: Gastric mucosal lesions occurred 0.5 h after C48/80 treatment and progressed at 3 h. Gastric mucosal blood flow decreased 0.5 h after C48/80 treatment but the decrease was recovered at 3 h. Gastric mucosal total AA, reduced AA, vitamin E, and adherent mucus concentrations decreased 3 h after C48/80 treatment. Gastric mucosal oxidized AA concentration remained unchanged after C48/80 treatment. Gastric mucosal NPSH concentration decreased 0.5 h after C48/80 treatment, but the decrease was recovered at 3 h. Gastric mucosal TBARS concentration and MPO activity increased 0.5 h after C48/80 treatment and further increased at 3 h. Serum total AA and reduced AA concentrations increased 0.5 h after C48/80 treatment and further increased at 3 h, while serum oxidized AA concentration increased at 0.5 h. Serum and gastric mucosal NOx concentrations increased 3 h after C48/80 treatment. AA administration to C48/80-treated rats at 0.5 h after the treatment prevented the gastric mucosal lesion progression and the changes in gastric mucosal total AA, reduced AA, vitamin E, adherent mucus, NOx, and TBARS concentrations and MPO activity and serum NOx concentration found at 3 h after the treatment dose-dependently. The AA administration to C48/80-treated rats caused further increases in serum total AA and reduced AA concentrations at 3 h after the treatment dose-dependently. CONCLUSION: Gastric mucosal AA plays a critical role in the progression of C48/80-induced acute gastric mucosal lesions in rats.

Animals↗

PubMed1995

Endotoxemia causes ileal mucosal acidosis in the absence of mucosal hypoxia in a normodynamic porcine model of septic shock.

OBJECTIVE: To evaluate the hypothesis that splanchnic ischemia and mucosal hypoxia are responsible for lipopolysaccharide-induced intramucosal acidosis in pigs. DESIGN: Prospective, randomized, unblinded study. SETTING: Surgical research laboratory at a large, university-affiliated medical center. SUBJECTS: Anesthetized, mechanically ventilated swine. INTERVENTIONS: Pigs were infused with lactated Ringer's solution (12 mL/kg/hr) and, starting at 30 mins, 25-mL boluses of dextran-70 (maximum 15 mL/kg/hr) to maintain cardiac output at 90% to 110% of the baseline value for each pig. Ileal mucosal hydrogen ion concentration was measured tonometrically. A segment of distal ileum was exteriorized, opened, and placed on a platform to permit measurement of mucosal PO2, using an array of Clark-type microelectrodes and a computerized data acquisition and analysis system. Mucosal perfusion was measured using laser-Doppler flowmetry. The control group (n = 4) received no further interventions. Pigs in the lipopolysaccharide group (n = 6) were infused with 150 micrograms/kg of Escherichia coli lipopolysaccharide over 60 mins. To assess the effect of mucosal acidosis on mucosal PO2 in nonendotoxemic animals, intramucosal hydrogen ion concentration, mucosal PO2, and mucosal perfusion were measured in pigs rendered hypercarbic through deliberate hypoventilation (hypercarbia group; n = 4). MEASUREMENTS AND MAIN RESULTS: Infusion of lipopolysaccharide resulted in a significant increase in intramucosal hydrogen ion concentration. However, in the lipopolysaccharide group, mucosal perfusion did not change significantly and mucosal PO2 increased significantly. In the hypercarbia group, hypercarbia was associated with significant increases in both intramucosal hydrogen ion concentration and mucosal PO2. CONCLUSIONS: Mucosal hypoxia is not responsible for lipopolysaccharide-induced mucosal acidosis in this normodynamic pig model of septic shock. A rightward shift of the oxyhemoglobin dissociation curve (the Bohr effect) can explain the increase in mucosal oxygenation observed in endotoxemic pigs.

Acidosis↗

PubMed1999

Preventive effect of teprenone on stress-induced gastric mucosal lesions and its relation to gastric mucosal constitutive nitric oxide synthase activity.

Recently, we demonstrated that teprenone, an anti-ulcer agent, exerts protective and preventive actions against water immersion restraint (WIR) stress-induced gastric mucosal lesions in rats both by inhibiting neutrophil infiltration into the gastric mucosal tissue and by preserving gastric mucus synthesis and secretion. In rats with WIR stress we have also found a decrease in gastric mucosal constitutive nitric oxide synthase (cNOS) activity and a drastic increase in gastric mucosal inducible nitric oxide synthase (iNOS) activity. The decrease in gastric mucosal cNOS activity is closely related to an increase in neutrophil infiltration into the gastric mucosa and a decrease in the level of gastric mucus. In this study of WIR-stressed rats, therefore, we examined whether the inhibitory actions of teprenone on neutrophil infiltration and decreases in mucus synthesis and secretion in the gastric mucosa of rats are related to the change in gastric mucosal cNOS activity during the development of gastric mucosal lesions. Pre-administration of teprenone (200 mg kg-1) prevented the decrease in gastric mucosal cNOS activity with attenuations of neutrophil infiltration into gastric mucosal tissues and decreased levels of gastric mucosal hexosamine, an index of gastric mucin, and adherent mucus in rats with 3 or 6 h of WIR stress. These preventive effects of teprenone on the gastric mucosal neutrophil infiltration and the decrease in gastric mucus levels in rats with WIR stress were completely reversed with inhibition of gastric mucosal cNOS activity by co-administration of NG-monomethyl L-arginine (L-NMMA), a non-selective NOS inhibitor. These results suggest that the inhibitory actions of teprenone on neutrophil infiltration and decreases in mucus synthesis and secretion in the gastric mucosa of rats with WIR stress are closely related to the maintenance of cNOS activity in the gastric mucosal tissue.

Animals↗

PubMed2003

Effect of mucosal suture on the healing of mucosal defect in laparoscopic intragastric surgery.

BACKGROUND: The efficacy of mucosal suturing for the healing of a mucosal defect in laparoscopic intragastric surgery (LIGS) for gastric lesions is not yet known. METHODS: We prospectively studied ten patients who underwent mucosal resection by LIGS for gastric tumors: four patients with early gastric cancer and six with gastric adenoma. Patients were randomly divided into two groups: group I (n = 5); patients who underwent mucosal resection by LIGS with mucosal defect suturing and group II (n = 5); patients who underwent mucosal resection by LIGS without mucosal defect suturing. We performed endoscopy on day 10, and 1 month, 2 months, and 3 months after the operation to observe the healing process of the mucosal defect. The ulcer stage by endoscopy was classified as active, healing, or scarring according to the classification of Sakita and colleagues. Patients were given an H(2)-blocker daily until the mucosal defect improved to the scarring stage. RESULTS: There were no significant differences in sex, age, tumor location, size of mucosal resection, or the incidence of Helicobacter pylori infection between groups I and II. The ulcer stages in group I were significantly lower than those in group II on day 10, and 1 month, 2 months, and 3 months postoperation. The medication cost (H2-blocker) in group I was significantly lower than that in group II. CONCLUSION: Mucosal defect suturing after mucosal resection by LIGS promotes more rapid healing of mucosal defects and reduces drug costs for patients.

Adenoma↗

PubMed2006

Mucosal acid causes gastric mucosal microcirculatory disturbance in nonsteroidal anti-inflammatory drug-treated rats.

The mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) suppress gastric mucosal blood flow is not fully understood, although the depletion of mucosal prostaglandin E2 has been proposed as one possible explanation. We investigated the role of gastric acid on gastric mucosal blood flow in NSAID-treated rats. A rat stomach was mounted in an ex vivo chamber, and gastric mucosal blood flow was measured sequentially in a 5-mm2 area of the gastric corpus using a scanning laser Doppler perfusion image system. Results showed that diclofenac (5 mg/kg s.c.) and indomethacin (10 mg/kg s.c.) did not affect gastric mucosal blood flow, although both strongly decreased mucosal prostaglandin E2 when saline was instilled into the gastric chamber. On replacement of the saline in the chamber with 100 mM hydrochloric acid, these drugs caused a decrease in gastric mucosal blood flow levels within 30 min. The specific cyclooxygenase (COX)-2 inhibitors celecoxib (50 mg/kg s.c.) and rofecoxib (25 mg/kg s.c.) did not affect mucosal prostaglandin E2 level, nor did they decrease gastric mucosal blood flow, even when hydrochloric acid was added to the chamber. Furthermore, measurement of vasoconstrictive factors present in the mucosa showed that endothelin-1 levels increased after administration of diclofenac s.c. in the presence of intragastric hydrochloric acid. This indicates that the presence of mucosal hydrochloric acid plays an important role in the NSAID-induced decrease in gastric mucosal blood flow, while the COX-1-derived basal prostaglandin E2, which is unlikely to control gastric mucosal blood flow itself, protects microcirculatory systems from mucosal hydrochloric acid.

Animals↗

PubMed2000

Gastric mucosal cell proliferation in ethanol-induced chronic mucosal injury is related to oxidative stress and lipid peroxidation in rats.

The oxygen free radicals-induced lipid peroxidation (LP) has been implicated in the pathogenesis of acute ethanol-induced gastric mucosal lesions. However, the role of LP in the generation of chronic gastric mucosal injury is unknown. We have developed a model of chronic mucosal injury induced by continuous ethanol ingestion for 5 days and characterized by marked alterations in plasma membranes from gastric mucosa. Therefore, LP was evaluated in this experimental model. Indicators of peroxidative activity, mucosal glutathione content, thymidine kinase activity (an index of cell proliferation), and histamine H2-receptor (H2R) binding constants were quantified in animals undergoing gastric mucosal damage. The effect of famotidine, a H2R antagonist that readily ameliorates the chronic mucosal injury, was also tested. Increased free radicals and LP levels were detected during gastritis; however, a second, higher peak of LP was noted in mucosal plasma membranes after ethanol withdrawal (recovery period). This further increase of LP coincided with active cell proliferation, decreased mucosal glutathione levels, and diminished specific cimetidine binding by H2R. Administration of famotidine accelerated the mucosal proliferative process, inducing the second lipoperoxidative episode sooner, and preserved the content of glutathione. In addition, LP correlated directly with cell proliferation and inversely with mucosal membrane cimetidine binding. In conclusion, LP seems to be involved in chronic ethanol-induced gastric mucosal injury. However, a further enhancement of plasma membrane LP occurred, associated with increased DNA synthesis and diminished cimetidine binding by membrane H2R. Therefore, increased LP could also participate in the compensatory mucosal proliferation initiated after ethanol withdrawal.

Animals↗

PubMed1995

Dual binding capacity of mucosal immunoblasts to mucosal and synovial endothelium in humans: dissection of the molecular mechanisms.

Lymphocytes continuously migrate throughout the body in search of antigens. Virgin lymphocytes recirculate freely between the blood and different lymphatic organs, whereas immunoblasts extravasate preferentially into sites similar to those where they initially responded to antigen. Tissue-specific extravasation of lymphocytes is largely controlled by distinct lymphocyte surface receptors that mediate lymphocyte binding to high endothelial venules (HEV). In the present study, the molecular mechanisms determining the specificity of human mucosal (lamina propria) lymphocyte binding to different endothelial recognition systems were analyzed. Mucosal immunoblasts adhered five times better than small mucosal lymphocytes to mucosal HEV. Importantly, mucosal immunoblasts also bound to synovial HEV almost as efficiently as to mucosal HEV, but they did not adhere to peripheral lymph node HEV. To study the impact of different homing-associated molecules in this dual endothelial binding, we used a gut-derived T cell line and freshly isolated mucosal immunoblasts. Both cell types expressed integrins alpha 4, beta 1, beta 7, and lymphocyte function associated antigen 1 (LFA-1), and were CD44 positive, but practically L-selectin negative. Binding of mucosal immunoblasts to mucosal HEV was almost completely abolished by pretreatment with anti-beta 7 monoclonal antibodies, but it was independent of alpha 4/beta 1 function. In contrast, alpha 4/beta 1 partially mediated immunoblast adherence to synovial HEV, whereas alpha 4/beta 7 had only a minor role in adherence of blasts at this site. CD44 and LFA-1 contributed to HEV-binding both in mucosa and synovium. Taken together, this is the first report that demonstrates a critical role for alpha 4/beta 7 in the binding of gut lymphocytes to mucosal venules in humans. Moreover, a hitherto unknown interaction between mucosal effector cells and synovial endothelial cells was shown to be only partially mediated by the currently known homing receptors. The dual endothelial binding capacity of mucosal blasts may help to explain the pathogenesis of reactive arthritis not uncommonly associated with inflammatory and infectious bowel disease.

Carrier Proteins↗

PubMed2005

Role of gastric mucosal ascorbic acid in gastric mucosal lesion development in rats with water immersion restraint stress.

We examined the role of gastric mucosal ascorbic acid (AA) in gastric mucosal lesion development in rats with water immersion restraint stress (WIRS). When fasted rats were subjected to WIRS for 1, 3 or 6 h, gastric mucosal lesions developed at 3 and 6 h. Gastric mucosal AA concentration decreased at 3 and 6 h after the onset of WIRS, while gastric mucosal non-protein SH concentration decreased at 1, 3, and 6 h and gastric mucosal vitamin E concentration decreased at 6 h. Gastric mucosal lipid peroxide concentration and myeloperoxidase activity increased at 3 and 6 h of WIRS. Pre-administration of AA (250 mg/kg) prevented gastric mucosal development with attenuation of the decreased gastric mucosal AA, non-protein SH and vitamin E concentrations, and the increased gastric mucosal lipid peroxide concentration and myeloperoxidase activity. These results suggest that gastric mucosal AA plays an important role in WIRS-induced gastric mucosal lesion development.

Animals↗

PubMed2006

Contributions of mucosal immune cells to methotrexate-induced mucositis.

The use of high doses of the anti-cancer drug methotrexate (MTX) is associated with intestinal damage. As a result, mucosal immune cells become increasingly exposed to a vast amount of microbial stimuli. We aimed at determining whether these cells are still functional during MTX treatment. Furthermore, we assessed if activation of the mucosal immune system would play a role in the pathogenesis of mucositis. A contributive role to mucositis for the adaptive immune system was established by showing that mucosal lymphocytes from MTX-treated mice secreted enhanced amounts of cytokines upon ex vivo polyclonal stimulation. Next, in vitro experiments revealed that macrophages were not affected by MTX in the capacity to produce tumor necrosis factor-alpha (TNF-alpha) and IL-10 after LPS exposure. Moreover, peritoneal macrophages from MTX-treated mice produced more IL-10 and TNF-alpha upon LPS stimulation, compared with cells derived from control mice. These data indicate a persistence of both innate and adaptive immune responses in this model. The clinical relevance of these findings was further established by the fact that LPS exposure prior to MTX treatment aggravated the course of mucositis. Furthermore, LPS-responsive mice recovered more slowly compared with LPS-unresponsive mice from MTX treatment. Finally, we found an increase in weight loss and intestinal damage upon MTX treatment in IL-10-deficient mice in comparison to wild-type controls, suggesting a protective role for IL-10 in mucositis. We conclude that mucosal immune responses remain resilient during MTX-induced mucositis. Whereas TNF-alpha production may contribute to mucosal damage, IL-10 may regulate by restricting excessive mucositis.

Animals↗

PubMed1998

Mucosal immunisation with papillomavirus virus-like particles elicits systemic and mucosal immunity in mice.

It has been shown previously that recombinant virus-like particles (VLPs) of papillomavirus can induce VLP-specific humoral and cellular immune responses following parenteral administration. To test whether mucosal administration of bovine papillomavirus type 1 (BPV1) VLPs could produce mucosal as well as systemic immune responses to VLPs, 50 micrograms chimeric BPV1 VLPs containing an HPV16 E7 CTL epitope (BPVL1/E7 VLP) was administered intranasally to mice. After two immunisations, L1-specific serum IgG and IgA were observed. L1-specific IgG and IgA were also found in respiratory and vaginal secretions. Both serum and mucosal antibody inhibited papillomavirus VLP-induced agglutination of RBC, indicating that the antibody induced by mucosal immunisation may recognize conformational determinants associated with virus neutralisation. For comparison, VLPs were given intramuscularly, and systemic and mucosal immune responses were generally comparable following systemic or mucosal delivery. However, intranasal administration of VLP induced significantly higher local IgA response in lung, suggesting that mucosally delivered HPV VLP may be more effective for mediating local mucosal immune responses. Intranasal immunisation with HPV6b L1 VLP produced VLP-specific T proliferative responses in splenocytes, and immunisation with BPVL1 VLP containing an HPV16 E7 CTL epitope induced E7-specific CTL responses. We conclude that immunisation with papillomavirus VLPs via mucosal and intramuscular routes, without adjuvant, can elicit specific antibody at mucosal surfaces and also systemic VLP epitope specific T cell responses. These findings suggest that mucosally delivered VLPs may offer an alternative HPV VLP vaccine strategy for inducing protective humoral immunity to anogenital HPV infection, together with cell-mediated immune responses to eliminate any cells which become infected.

Administration, Intranasal↗

PubMed2005

Type 1 immunity provides both optimal mucosal and systemic protection against a mucosally invasive, intracellular pathogen.

It has been hypothesized that optimal vaccine immunity against mucosally invasive, intracellular pathogens may require the induction of different types of immune responses in mucosal and systemic lymphoid tissues. Mucosal type 2/3 responses (producing interleukin-4 [IL-4], IL-6 and/or transforming growth factor beta) could be necessary for optimal induction of protective secretory immunoglobulin A responses. On the other hand, systemic type 1 responses (including gamma interferon [IFN-gamma], tumor necrosis factor alpha, and optimal cytotoxic T-cell responses) are likely to be critical for protection against the disseminated intracellular replication that occurs after mucosal invasion. Despite these predictions, we recently found that vaccines inducing highly polarized type 1 immunity in both mucosal and systemic tissues provided optimal mucosal and systemic protection against the protozoan pathogen Trypanosoma cruzi. To further address this important question in a second model system, we now have studied the capacity of knockout mice to develop protective immune memory. T. cruzi infection followed by nifurtimox treatment rescue was used to immunize CD4, CD8, beta2-microglobulin, inducible nitric oxide synthase (iNOS), IL-12, IFN-gamma, and IL-4 knockout mice. Despite the previously demonstrated importance of CD4(+) T cells, CD8(+) T cells, and nitric oxide for T. cruzi immunity, CD4, CD8, and iNOS knockout mice developed mucosal and systemic protective immunity. However, IL-12, IFN-gamma, and beta2-microglobulin-deficient mice failed to develop mucosal or systemic protection. In contrast, IL-4 knockout mice developed maximal levels of both mucosal and systemic immune protection. These results strongly confirm our earlier conclusion from studies with polarizing vaccination protocols that type 1 immunity provides optimal mucosal and systemic protection against a mucosally invasive, intracellular pathogen.

Animals↗

PubMed2002

Mucosal immunity--basic principles, ontogeny, cystic fibrosis and mucosal vaccination.

The mucosal immune system is an integral part of the whole-body immune system, however its regulation, maturation and function are to a great degree independent. Mucosal lymphoid tissue is the largest immune organ of the body, that stands in the first line of defence against foreign invaders. The goal of the immune system is immunity, however immunologic unresponsiveness (tolerance) is a key feature of the mucosal immune system, because the organism must tolerate thousands of ingested and inhaled harmless food and bacterial antigens. The phenomenon of oral tolerance is the unique feature of the mucosal immune system. If abrogated, severe autoimmune diseases like Crohn's disease, ulcerative colitis or coeliac sprue can develop. The quality of mucosal immune responses during newborn and infant age strongly influences the immune reactivity later in life. The most important factors influencing the development of mucosal immune reactivity are the feeding practices and microbial colonization. Manipulation of the mucosal immune system offers interesting possibilities to prevent infection as well as autoimmune diseases directly in the affected tissue, without participation of the whole-body immune system. In this review we present the most recent basic information about the mechanisms of mucosal immunity, ontogeny of mucosal immunity, mucosal tolerance and immunisation and the role of mucosal immunity in an inherited disease in which the main battlefield is the lung mucosa-cystic fibrosis.

Child Development↗

PubMed1988

Gastric mucosal repair in the cat: role of the hyperemic response to mucosal damage.

This study concerns the significance for the mucosal repair process of the gastric mucosal hyperemic response after mucosal damage caused by 2 M NaCl. Celiac artery blood flow was measured by Doppler ultrasound and stomach arterial inflow was either left undisturbed or reduced in a controllable fashion by tightening a vessel loop around the celiac artery immediately after mucosal exposure to 2 M NaCl or 150 mM NaCl. The stomach lumen was perfused with saline at pH 1.00 before and after exposure to 2 M NaCl. Gastric mucosal blood flow increased after exposure to 2 M NaCl, and 90 min after mucosal exposure to 2 M NaCl the mucosal surface showed nearly complete restitution of the surface epithelium. In all animals in which mucosal hyperemia was restricted by reducing celiac artery blood flow by 60% after mucosal damage, extensive gastric erosions were present. Similar reduction of celiac artery blood flow in control animals without mucosal damage did not produce visible lesions, and the stomachs proved to be normal by microscopy. These findings show that the gastric mucosal hyperemic response after damage is important for protection of the damaged mucosa during restitution of the gastric surface epithelium.

Animals↗