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Results for “immunomodulation”

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At least 613 records · Page 34Linked to original sources

PubMed1995

In vivo study of the immunomodulating activity of OM-85 using the plaque-forming cells technique (PFC) in mice.

The activity of increasing oral doses of the bacterial extract OM-85 was determined by using the plaque-forming cells assay in mice. The results showed that the oral administration of OM-85 significantly increased the number of splenic antibody-secreting cells against sheep red blood cells (antigen) compared with controls. A maximal response was reached between 400 and 800 mg/kg body weight, and was reproducible with the different batches of OM-85 used. This study indicates that the oral administration of the immunomodulator allows the activation of splenic B-lymphocytes, probably through the gut-associated lymphoid tissue.

Adjuvants, Immunologic↗

PubMed1989

A phase I study of immunostimulation and toxicity in patients with colorectal carcinoma using the immunomodulator 3,6-bis(2-piperidinoethoxy) acridine trihydrochloride (CL 246738).

Seventeen patients with residual or recurrent colorectal carcinoma were given a new synthetic immunomodulator [3,6-bis(2-piperidinoethoxy) acridine trihydrochloride CL246738) as part of a phase I clinical trial. No patients had undergone previous immunotherapy or chemotherapy. Detailed immunological studies including interferon levels, interleukin 2 levels, natural killer cell function, mitogen responses of lymphocytes, immunoglobulin levels and lymphocyte subpopulation levels were analysed in the patients who received this drug in an attempt to find out whether there was any biological activity identifiable in humans. None of the subjects showed any significant increases in post treatment values of the immunological parameters studied. Toxic effects of the drug at high doses included nausea, diarrhoea and decreased levels of consciousness. In conclusion, no immunological effects were identified following the administration of CL 246738 in human subjects with recurrent or residual colorectal cancer.

Acridines↗

PubMed1989

Relationship of the hypothalamic-pituitary-adrenal axis with chemically induced immunomodulation. I. Stress-like response after exposure to T-2 toxin.

T-2 toxin (T-2), a trichothecene mycotoxin, produced by several members of the genus Fusarium is a cytotoxic feed contaminant and has been shown to by immunomodulatory. It is suspected that T-2 associated immunomodulation is mediated partly through the hypothalamic-pituitary-adrenal (HPA) axis. T-2, prepared in 4% ethanol/corn oil, was administered orally to male CD-1 mice. Endotoxemia was evident 24 h after a single, oral exposure to T-2. Blood levels of corticosterone, indicative of the stress-response, increased 24 h after T-2 exposure. Hypothalamic norepinephrine and serum corticosterone levels increased in a dose-related manner after 2 weeks of T-2 exposure. Endotoxin, detected in the serum of animals exposed to 2.5 mg/kg T-2 for 1 week, was not associated with bacteremia. Neither endotoxin nor bacteremia were detectable after 2 or 4 weeks of T-2 exposure. Exposure to 2.5 mg/kg T-2 also affected several organs. The forestomach was ulcerated, with lymphocytic infiltration, epithelial proliferation, and hyperkeratinization. Increased spleen weight was associated with a proliferative red pulp. No histological changes were observed in the enlarged liver. Gastritis has been associated with increased corticosteroid production; cortical depletion and reduced mass of the thymus are phenomena attributable to increased corticosteroid levels. An increased corticosteroid level has been associated with thymic involution leading potentially to decreased T-dependent antibody response, a known effect of T-2.

Adjuvants, Immunologic↗

PubMed1989

Immunomodulation by behavioural conditioning.

The contemporary surge in studies of behaviourally conditioned immunomodulation following Ader and Cohen (1975) was preceded by Pavlovian conditioning conducted in the Soviet Union during the 1920s and 1950s. Data from these studies provided a tenable hypothesis for immunomodification using classical conditioning processes. In particular a variant of Pavlovian conditioning, the conditioned taste aversion (CTA) paradigm, has proved very robust; here a novel gustatory experience (CS) is paired with an aversive physiological event (UCS) and subsequent gustatory avoidance of the CS alone is measured. Similar procedures have also been successfully applied to the conditioned alteration of cellular immune responses. Studies demonstrating behaviourally conditioned effects on the immune system are reviewed. More recently, conditioned immunoenhancement studies have demonstrated that taste aversion can induce a conditioned increase in the helper: suppressor T cell subset ratio in rats, and a depressed DTH response in mice. Mediating mechanisms for the conditioned effects are examined, in particular the roles of adrenocorticotropin (ACTH) and beta-endorphin (BEP), and the routes of communication between the CNS and immune system. Clinical applications of immunomodification may also be demonstrated by the potential therapeutic efficacy of both conditioned immunosuppression and immunoenhancement.

Animals↗

PubMed1992

Anti-infectious effect of C granulosum-derived P40 immunomodulator given by aerosolization and intranasal instillation.

It is known that C granulosum-derived P40 immunomodulator displays strong anti-microbial effects in mice by the intravenous route. Since microbial contamination of humans occurs in many instances via the airways, the effect of P40 on infections was investigated when it was given intranasally or by aerosolization. In order to augment its bioavailability, P40 was derivatized by coupling with polylysine chains (P40-PL). The results showed that P40-PL exercised a significant protective effect, both by the intranasal route and by aerosolization on both influenza and K pneumoniae infections produced by aerosolization or intranasal instillation. Stimulation of the phagocytic capacity of alveolar macrophages by these types of treatment is likely to account for the increased resistance of mice toward microbial infections.

Adjuvants, Immunologic↗

PubMedDate not supplied

Immunomodulation with P40, an insoluble delipidated fraction of Corynebacterium granulosum. I.--Immune response to sheep red blood cells.

The immunological responses to sheep red blood cells (SRBC) were evaluated in mice in order to study the immunomodulating effects of an insoluble fraction of Corynebacterium granulosum, designated P40. A single intravenous (IV) injection of 50 micrograms or more of P40 was able to stimulate the reticulo-endothelial system, as measured by the spleen index. A single IV injection of 250 micrograms of P40, given seven days prior to IV sensitization of groups of mice with varying doses of SRBC, was able to amplify both humoral and cellular immune responses. Lower doses of P40 given subcutaneously (SC) were able to potentiate delayed-type hypersensitivity (DTH) to SRBC. Potentiation depends on the route, dose and time of the P40 injection in relation to the time and route of sensitization. A bimodal activity of P40 was observed: one peak was noted with SRBC were mixed with P40, and a second peak occurred when P40 was injected at the same site four to five days prior to immunization. Maximal potentiation was achieved when SRBC were introduced SC together with 5 micrograms of P40. DTH reached a higher level in animals immunized under the influence of P40; however, the kinetics of the development and decay of DTH were the same in treated and non-treated mice. Immunopotentiation was demonstrated by passive transfer: using the same number of spleen cells from treated or non-treated immune mice, higher DTH reactions were observed in normal recipients when they received spleen cells from P40-treated donor mice. Immunopotentiation seemed to act by increasing the number of committed lymphocytes and not by augmenting the number of accessory cells, since adoptive transfer of DTH by immune cells was not different in normal or P40-treated recipients.

Adjuvants, Immunologic↗

PubMed1990

Phospholipase A2, an in vivo immunomodulator.

Arachidonic acid (AA) can be released from membrane phospholipids by the action of phospholipase A2 (PLA2). There is evidence that unsaturated fatty acids, particularly AA, released from membrane phospholipids are required to activate the respiratory burst of macrophages. The data reported here indicate that peritoneal macrophages harvested 30 min after i.p. injection of PLA2 can phagocytose Candida albicans more efficiently and emit more chemoluminescence (CL) than normal cells when stimulated by zymosan. PLA2 injection also enhances the CL of peritoneal cells from mice already stimulated by immunomodulators such as trehalose dimycolate (TDM), bestatin, or oncostatic drugs such as aclacinomycin (ACM). CL is not sensitive to potassium cyanide (KCN), but is inhibited by catalase, superoxide dismutase (SOD), nordihydroguaiaretic acid (NDGA) and high doses of indomethacin (10(-3) M). In vivo PLA2 treatment stimulates the synthesis of both cyclooxygenase and lipoxygenase derivatives of AA metabolism (PGE2, 6-keto, PGF1 alpha TXB2 and LTC4). Inhibitors of AA metabolism (NDGA, indomethacin) modulate the production of free oxidizing radicals in this experimental model, partly because of their effect on AA metabolism, as determined by the measuring immunoreactive products. However, this work indicates that the effects of these inhibitors, which have been extensively used in CL studies, should be interpreted with caution, since their specificity for AA metabolism is relative.

Adjuvants, Immunologic↗

PubMed1994

Treatment of autoimmune disease by immunomodulation through extracorporeal elimination and intravenous immunoglobulin.

If customary drug mediated immunosuppressive therapy leads to intolerable side effects or is inefficient, extracorporeal elimination and untargeted or targeted immunoglobin therapy modulating the immune response are taken into consideration for the treatment of patients with autoimmune diseases. Both elimination and immunoglobulin therapy, are not alternatives but appear to act complementary, if sequentially applied. Selective immunoadsorption is increasingly applied for extracorporeal elimination and is able to replace plasma exchange therapy. Both, hydrophobic interaction chromatography and affinity chromatography are effective in given clinical conditions. Therapeutic affinity chromatography appears to be superior to hydrophobic interaction chromatography, if an effective, rapid elimination of the disease promoting agent is desired. Experience with therapeutic chromatography collected in the past, indicates that a rapid elimination of immunoglobulins and the subsequent intravenous infusion of 7S immunoglobulin is superior to elimination or untargeted immunomodulation alone. These experimental approaches lead to an extension of the available treatment modalities. However, controlled trials rather than anecdotal reports are needed, to provide substantial information.

Adsorption↗

PubMed1993

Involvement of T lymphocytes in curative effect of a new immunomodulator OM 163 on rat colon cancer metastases.

In a model of colon cancer in syngeneic rats, a new immunomodulator, OM 163, induced the complete disappearance of peritoneal carcinomatosis (nodules measuring 1-5 mm) in 41 out of 82 rats. Those results were confirmed in a survival experiment in which 3 out of 10 treated rats died free of tumour 10, 18 and 28 months after the tumour cell injection while all the untreated control rats died of their tumours within 3 months. OM 163 had a systemic effect, since injected intraperitoneally it completely inhibited the growth of lung metastases in 13 out of 20 rats. The antitumour effect of OM 163 was also observed in two rat strains on original tumours. Lymphocyte infiltration was observed in the tumours mainly constituted of CD4+ and CD8+ cells. The treatment had no effect in nude rats, confirming the involvement of T lymphocytes. Furthermore, rats cured by OM 163 were protected against a second challenge of tumour cells and in a Winn's assay, splenocytes from cured rats protected normal rats against tumour cells.

Adjuvants, Immunologic↗

PubMed1994

The immunomodulator LS-2616 (linomide) more effectively than sensitization of the donor enhances graft-versus-host reaction after small bowel transplantation.

The effects of the immunomodulating substance LS-2616 (linomide) on graft-versus-host reaction (GVHR) were investigated in a semi-syngeneic small bowel transplantation model. The entire bowel of Lewis donors were transplanted heterotopically into (Lewis x BN) F1 hybrids. Both untreated animals and animals treated with LS-2616, in a daily dose of 160 mg/kg, developed a lethal GVHR. The median survival time in untreated animals was 14.5 days while in LS-2616 treated animals it was just eight days (p < 0.01). LS-2616 in combination with cyclosporin A (CyA), 15 mg/kg given orally on days 0-20, did not seem to alter the survival times compared with CyA treatment alone; 56% of the animals treated with CyA survived for more than 100 days and after combined treatment with CyA/LS-2616 there were 50% permanent survivors. Also the effect of earlier sensitization of the donor on the course of GVHR was investigated. Hearts from BN rats were transplanted heterotopically to the neck vessels of Lewis rats. The hearts were rejected on about day six; five days later the bowels were harvested and transplanted into (Lewis x BN) F1 hybrids. The median survival time in this group was 12.5 days. Taken together our results, in combination with earlier findings, suggest that, at the level of effector mechanisms, GVHR is not an exact mirror image of rejection. Also, LS-2616 appears to be a useful tool for further studies of the mechanisms of action of GVHR.

Adjuvants, Immunologic↗

PubMed2003

Inappropriate initial antimicrobial therapy and its effect on survival in a clinical trial of immunomodulating therapy for severe sepsis.

PURPOSE: To examine the effect of inappropriate initial antimicrobial therapy on the prognosis of patients with sepsis who were enrolled in a clinical trial of an immunomodulating agent conducted in 108 hospitals in North America and Europe. METHODS: We assessed initial antimicrobial choice and results of microbiologic cultures in 904 patients who had microbiologically confirmed severe sepsis or early septic shock. If a patient did not receive at least one antimicrobial agent to which the causative microorganisms were susceptible within 24 hours from the diagnosis of severe sepsis, then the initial antimicrobial treatment was considered to be inappropriate. A propensity score that adjusted for factors associated with inappropriate antimicrobial treatment was calculated and included in multivariable models to adjust for confounding. RESULTS: A total of 468 patients (52%) had documented bloodstream infection, and 211 patients (23%) received inappropriate initial antimicrobial therapy. Characteristics associated with inappropriate treatment were study enrollment in Europe, admission to surgery, nosocomial infection, infection with multiresistant microorganisms, and fungal or polymicrobial infection (all P <0.05). The 28-day mortality was 24% (168/693) for patients in the adequately treated group versus 39% (82/211) for patients receiving inappropriate initial antimicrobial therapy (P <0.001). After adjusting for comorbid conditions, severity of illness, site of infection, and the propensity score, inappropriate antimicrobial therapy was independently associated with increased mortality (odds ratio = 1.8; 95% confidence interval: 1.2 to 2.6). CONCLUSION: In a large cohort of patients with microbiologically confirmed severe sepsis, appropriate initial antimicrobial therapy was an important determinant of survival. New approaches aimed at improving detection and treatment of early sepsis are needed.

Aged↗

PubMed2005

Intravenous immunoglobulin for immunomodulation of systemic lupus erythematosus.

Intravenous immunoglobulin (IVIg) is used for replacement therapy in immunodeficiency states and for immunomodulation of various autoimmune diseases. Several case reports and series support a beneficial role of IVIg in systemic lupus erythematosus (SLE), both as salvage immunotherapy and in control of disease activity in general and amelioration of classical disease manifestations. Further, lupus nephritis can also be treated usually successfully with IVIg. A few questions remain unanswered as to the appropriate therapeutic dosage and the clinical manifestations that can be best treated with IVIg.

Glomerulonephritis↗

PubMed2005

Resistance to influenza A virus infection by antigen-conjugated CpG oligonucleotides, a novel antigen-specific immunomodulator.

Oligodeoxynucleotides (ODN) containing CpG motifs (CpG) act as modulators that bias the immune response towards a Th1-dominant phenotype. To investigate this effect further, we examined the protective effects of a covalently linked conjugate between CpG-ODN and HA-2kd antigen in mice infected with influenza A virus. The conjugated form of CpG-ODN and HA-2kd was more efficient in regulating influenza A virus than the unconjugated mixture of CpG-ODN and HA-2kd. The antigen-conjugated CpG-ODN induced an immune response with a Th1-dominant cytokine pattern characterized by the secretion of high levels of HA-2kd-specific interferon-gamma and IgG2a (Th1), which were only slightly induced by HA-2kd alone. These findings support the use of CpG-ODN-Ag conjugates as novel Ag-specific immunomodulators and suggest that CpG-ODN-HA-2kd might be a promising immune therapy for patients with influenza virus.

Animals↗

PubMed2006

The immunomodulator AS101 induces growth arrest and apoptosis in multiple myeloma: association with the Akt/survivin pathway.

Multiple Myeloma (MM) is a clonal B-cell malignancy affecting both the immune and the skeletal systems, and accounts for 10% of all hematological cancers. The immunomodulator ammonium trichloro (dioxoethylene-O,O') tellurate (AS101) is a non-toxic compound which has direct anti-tumoral properties in several tumor models. The present study examined the anti-tumoral activity of AS101 in MM by targeting the Akt/Survivin signaling pathway, crucial for survival. We showed that AS101 inhibites cell proliferation and colonies formation of MM cell lines, in a dose-dependent manner. AS101 induced G(2)/M growth arrest and increased both cyclin-dependent kinase inhibitor p21(waf1) protein levels and Cdk1 (p34(cdc2))-inhibitory phosphorylation. Longer incubation of MM cells with AS101 resulted in accumulation of apoptotic cell population and in increased caspase 9, 3 and 7 activities. We also showed that AS101 down-regulated Akt phosphorylation and decreased expression of the inhibitor of apoptosis, survivin. Since Akt and survivin are potentials targets for MM therapy, we suggest that AS101, currently being used in clinical studies, may have therapeutic implications in myeloma and other hematopoietic malignancies.

Adjuvants, Immunologic↗

PubMed2004

Increased interleukin-10 associated with low IL-6 concentration correlated with greater survival rates in mice infected by rabies virus vaccinated against it and immunomodulated with P. acnes.

Macrophage activity, cytokines serum concentration, serum neutralizing antibodies and lethality by rabies were evaluated in swiss mice experimentally infected with street rabies virus and submitted or not to antirabies vaccination and immunomodulation with P. acnes. Animals were killed at different times and serum was collected in order to evaluate cytokines concentration; peritonial and splenic macrophages were collected for macrophage activity evaluation. Greater survival rates higher IL-10 and low IL-6 serum concentration were observed in vaccinated animals treated using P. acnes.

Animals↗

PubMed2005

Identification of prolactin as a novel immunomodulator on the expression of co-stimulatory molecules and cytokine secretions on T and B human lymphocytes.

We investigate the immunomodulator role of prolactin (PRL) on CD4+ and B cell activation from healthy subjects in comparison with hyperprolactinemic patients. Peripheral blood mononuclear cells, CD4+ or B cells, purified, were cultured under different conditions, as follows: with mitogen, without stimulus, with different concentrations of human PRL, with unspecific mitogen plus PRL, or with antibodies against PRL. The results revealed that PRL is produced by lymphocytes, the expression of CD69 and CD154 molecules, and interleukin secretions depend partially on the autocrine PRL, this is supported by the findings that secretions of IL-2, IFNgamma, and co-stimulatory molecule expression were markedly reduced when autocrine PRL was blocked with anti-PRL antibodies. Furthermore, PRL activity was only observed during the first 2 h after activation. In contrast, B cell culture did not show any alteration by adding or blocking PRL in the expression of CD40 and CD86 in both groups: healthy subject and hyperprolactinemic patients.

Adult↗

PubMed2004

Immunomodulating agents.

Inflammation involves a universally recognized, although incompletely understood, cascade of molecular events orchestrated by lymphokines and other innate biochemicals of immunity. Repeated or extended contact with immunogenic agents results in adaptive immunity involving antigen-induced events that stimulate down-stream immune cells and result in expansion of the inflammatory cascade. When immunogenic stimulation persists or autoregulatory immune mechanisms go awry, however, adaptive immunologic events can result in immune-mediated processes detrimental to systemic or organ-specific homeostasis. Because of the complexities of immunologic events, the potential side effects of long-term corticosteroid therapy, and the focused spectrum of most conventional nonsteroidal anti-inflammatory agents (centered on arachidonic acid-related mechanisms), a variety of other chemotherapeutic immunosuppressive agents have assumed an increasingly prominent therapeutic role in veterinary ophthalmology in the management of chronic ocular inflammatory diseases. In addition, nonimmunosuppressive immunomodulating agents (ie, immuno-stimulants or immunorestoratives) may be used as adjunctive therapies in the management of ocular or visual system diseases.

Adjuvants, Immunologic↗

PubMed2005

Upregulation of carp GDNF mRNA by the immunomodulator AS101.

Although the glia derived neurotrophic factor (GDNF) is defined as a molecule that maintains neuronal cells, it possesses a range of functions outside the nervous system. For example, it is essential for uretric branching in kidney morphogenesis and for regulating the differentiation of stem cells during spermatogenesis, cardiac, hair follicle and vascular differentiation and the maintenance of immune cells. In the present work, the presence of GDNF in carp peripheral blood leukocytes (PBL) and head kidney cells (HK) was evidenced and its evolutionary importance in both neural and immune systems development was suggested. Using the northern-blot technique, we could observe the expression of two different transcripts of this gene. GDNF upregulation was detected using semi-quantitative PCR, following ex vivo treatment of PBL and HK cells with the immunomodulator AS101 which was previously shown to inhibit IL-10 and to up-regulate GDNF protein levels in human SVG astrocyte cell line, in 6-OHDA hemi-parkinsonian mice in vivo and in rat glomerular mesengial cells in vitro.

Amino Acid Sequence↗