Biomedical subjects

Yvette Mándi

Publications and source records attributed to Yvette Mándi.

At least 19 recordsLinked to original sources

PubMed2006

The role of histamine in the intracellular survival of Mycobacterium bovis BCG.

The course and outcome of infection with mycobacteria are determined by a complex interplay between the immune system of the host and the survival mechanisms developed by the bacilli. Histamine plays an important role in various processes, including cell division, metabolism, and apoptosis, and it modulates innate and adaptive immune responses. In the present study we investigated the intracellular survival of Mycobacterium bovis BCG in murine bone-marrow macrophages isolated from wild-type (WT) and histidine-decarboxylase knock-out [HDC (-/-)] mice. Mycobacterial titers were significantly higher in the HDC (-/-) macrophages as compared with the WT cells. M. bovis BCG growth in WT macrophages could be enhanced by pyrilamine and cimetidine. Exogenously added histamine decreased the intracellular counts of M. bovis BCG in HDC (-/-) macrophages. Infection of activated macrophages with M. bovis BCG elicited apoptosis, but there was no significant difference between the WT and the HDC (-/-) cells. These bacilli induced comparable levels of tumor necrosis factor-alpha production in the WT and the HDC (-/-) macrophages. M. bovis BCG stimulated interleukin-18 (IL-18) production in the macrophages from WT mice, but not in the HDC (-/-) cells. Exogenously added IL-18 decreased the titers of intracellular mycobacteria in HDC (-/-) cells. In conclusion, these data implicate histamine in the intracellular survival of M. bovis BCG. The cellular control mechanisms restricting the growth of M. bovis BCG are complex and involve H1 and H2 receptor-mediated events. Histamine might be an important mediator of M. bovis BCG-induced IL-18 production, which in turn contributes to immune protection.

Animals↗

PubMed2006

Surgical management and complex treatment of infected pancreatic necrosis: 18-year experience at a single center.

Infected pancreatic necrosis (IPN), the most severe form of acute pancreatitis, is responsible for most cases of pancreatitis-related morbidity and mortality. Since 1986, 220 patients with IPN have been treated. The surgical treatment was performed on average 18.5 days (range, 8-25 days) after the onset of acute pancreatitis and consisted of wide-ranging necrosectomy, combined with widespread drainage and continuous lavage. In 108 of the 220 cases, some other surgical intervention (distal pancreatic resection, splenectomy, total pancreatectomy, cholecystectomy, colon resection, etc.) was also performed. Following surgery, the supportive therapy consisted of immunonutrition (glutamine and arginine supplementation) and modification of cytokine production with pentoxifylline and dexamethasone. Continuous lavage was applied for an average of 44.5 days (range, 21-95 days), with an average of 9.5 L (range, 5-20 L) of saline per day. The bacteriologic findings revealed mainly enteral bacteria, but Candida infection was also frequently detected (21%). Forty-eight patients (22%) had to undergo reoperation. The overall hospital mortality was 7.7% (17 patients died). In our experience, IPN responds well to adequate surgical treatment, continuous, longstanding widespread drainage and lavage, together with supportive therapy consisting of immunonutrition and modification of cytokine production, combined with adequate antibiotic and antifungal medication.

Adult↗

PubMed2005

Vesicular stomatitis virus induces apoptosis in the Wong-Kilbourne derivative of the Chang conjunctival cell line.

BACKGROUND: Virotherapy represents a novel therapeutic modality for the treatment of malignant diseases. Vesicular stomatitis virus (VSV) has been shown to exert antitumor effect in several tumor types. Since the potential oncolytic activity of VSV has not yet been evaluated in epithelial tumors of the conjunctiva, we set out to investigate the susceptibility of the immortalized Wong-Kilbourne derivative of the Chang conjunctival cell line (WK) to VSV and analyze the role of apoptosis in VSV-mediated induction of cell death. METHODS: WK cells were infected with VSV at various multiplicities and maintained for different periods of time. VSV-infected cells were analyzed by inverted microscopy for the development of cytopathic effects (CPE). Virus replication was measured by indirect immunofluorescence assay, Western blot analysis and plaque titration. The apoptotic response of the infected cells was quantitated by ELISA detecting the enrichment of nucleosomes in the cytoplasm. Western blot analysis was used to determine the levels of Bcl-2 and Bax proteins. RESULTS: The WK cell line was highly permissive to VSV replication and was highly susceptible for the CPE of this virus. VSV infection elicited the apoptotic death of WK cells. Mock-infected cells exhibited endogenous expression of Bcl-2 and p21 Bax proteins. VSV infection caused a significant decrease in the expression level of Bcl-2. Moreover, in parallel with a slight decrease in the level of p21 Bax, p18 Bax protein accumulated in VSV-infected WK cells. CONCLUSIONS: VSV is a powerful inducer of apoptosis in immortalized WK cells. The VSV-mediated alterations in the expressions of Bcl-2 and Bax proteins may play important roles in the apoptotic responses of infected cells and may also sensitize to other apoptotic stimuli. This virus may possess oncolytic activity in epithelial tumors of the conjunctiva.

Apoptosis↗

PubMed2005

Polymorphism of the heat-shock protein gene Hsp70-2, but not polymorphisms of the IL-10 and CD14 genes, is associated with the outcome of Crohn's disease.

OBJECTIVE: In Crohn's disease (CD) a Th-1 dominant immune reaction is induced, which could be associated with genetic predisposition. Several previous studies have investigated the roles of CD14, heat-shock protein (Hsp)70 and IL-10 gene polymorphisms in the development of the disease. The results are contradictory and inter-racial differences are implicated. Therefore, this phenomenon was evaluated in well-documented Caucasian patients with CD in order to verify the clinical importance of these polymorphisms. MATERIAL AND METHODS: The genomic DNA of 133 patients with CD and that of 75 healthy controls were examined. CD was divided into subgroups according to the Vienna classification. An arbitrary classification system based on disease severity was also applied, which was determined according to the therapeutic intervention. The CD14 (-159 C-->T) promoter gene polymorphism was investigated by melting-point analysis. The IL-10 (-1082 G-->A) and Hsp70-2 (1267 A-->G) gene polymorphisms were detected by RFLP (restriction fragment length polymorphism). RESULTS: None of the allele frequencies of the examined polymorphisms differed significantly between the patient and control populations. Neither the CD14 nor the IL-10 polymorphisms exhibited any correlation with the development or with the progression of the disease. With regard to Hsp70-2 gene polymorphism, those patients who carry at least one A allele have a significantly lower probability of the need for surgical intervention. CONCLUSIONS: Allele A of the Hsp70-2 gene may be associated with a less severe form of CD, suggesting the clinical value of the genotype assessment. The genetic determination of the defense mechanisms in CD appears to be associated with the polymorphism of the Hsp70-2 gene rather than that of the CD14 or IL-10 genes.

Adult↗

PubMed2005

Polymorphism of the TNF-alpha, HSP70-2, and CD14 genes increases susceptibility to severe acute pancreatitis.

OBJECTIVES: Proinflammatory cytokines and heat shock proteins play fundamental roles in the pathogenesis of acute pancreatitis. We studied whether polymorphisms of the tumor necrosis factor alpha (TNF-alpha), heat shock protein 70-2 (HSP70-2), and CD14 genes correlate with the severity of acute pancreatitis. METHODS: Patients with acute pancreatitis (n = 77) of mixed etiology were grouped according to the severity of the disease on the basis of the Ranson scores. Healthy blood donors (n = 71) served as controls. TNF-alpha-308 polymorphism was determined by NcoI RFLP, HSP70-2 polymorphism by PstI RFLP, and CD14-159 polymorphism by melting point analysis. RESULTS: There was a moderate increase in the frequency of the TNF1/2 genotype (P = 0.046) among patients with severe acute pancreatitis as compared with those with mild disease. A more significant increase was observed in the frequency of the HSP70-2 G allele between groups of patients with mild or severe pancreatitis (18.9% vs. 53%; P < 0.001). Conversely, the A/A genotype was markedly more frequent among the patients with mild pancreatitis (P < 0.0001). There was no significant correlation between CD14-159 promoter polymorphism and the severity of pancreatitis. CONCLUSION: High frequencies of the HSP70-2 G and the TNF-alpha -308 A alleles were associated with risk of severe acute pancreatitis. Genotype assessments may be important prognostic tools to predict disease severity and the course of acute pancreatitis. Therefore, genotype assessments may also be used to guide treatment or to identify risk populations for severe acute pancreatitis.

Acute Disease↗

PubMed2005

Clinical importance of transforming growth factor-beta but not of tumor necrosis factor-alpha gene polymorphisms in patients with the myelodysplastic syndrome belonging to the refractory anemia subtype.

OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) are cytokines that play key roles in the myelodysplastic syndrome (MDS). There have been several reports on the presence of genetic polymorphisms in the DNA sequence encoding the leader sequence of the TGF-beta1 protein, located in codon 10 in exon 1 and in the -308 promoter region of TNF-alpha. The objective of this study was to investigate the association between TNF-alpha and TGF-beta1 gene polymorphisms and the susceptibility to MDS and the progression of the disease among patients with MDS belonging to the refractory anemia (RA) subtype. METHODS: The diagnosis of MDS (n = 50) was based on the FAB criteria. The TNF-alpha genotypes were analyzed by PCR-RFLP and the TGF-beta genotypes were analyzed using an amplification refractory mutation system. RESULTS AND CONCLUSIONS: Compared with healthy control subjects, patients with RA showed no significant deviations in genotype or allele frequencies of TNF-alpha. The TT homozygosity at codon 10 of TGF-beta1 was significantly higher among patients with bi- or pancytopenia (severe group) than in the patients with anemia only (mild group; odds ratio = 6.99, p = 0.003). These findings suggest that the TGF-beta1 gene polymorphism in codon 10 and the -308 TNF-alpha gene polymorphism do not predispose to the development of RA, but the TGF-beta1 gene polymorphism may affect disease progression.

Adult↗

PubMed2005

Genetic polymorphisms in patients with myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is a family of clonal disorders characterized by dyshematopoiesis and susceptibility to acute myelogenous leukemia. Tumor necrosis factor-a (TNF-alpha) and transforming growth factor-beta (TGF-beta) are cytokines that play key roles in the pathogenesis of MDS. There have been several reports on the presence of genetic polymorphisms in the DNA sequence encoding the leader sequence of the TGF-beta protein, and in the -308 promoter region of TNF-alpha. The association between TNF-alpha and TGF-beta1 gene polymorphism and the susceptibility to MDS and the progression of the disease was investigated. As compared with healthy control subjects (n = 74), patients with MDS (n = 55) showed no significant deviations in genotype or allele frequencies of TNF-alpha. Similarly, there were no differences in the distribution of TNF-alpha genotypes between the MDS patients with only anemia (mild group) and those with bi- or pancytopenia (severe group). On the other hand the TT homozygosity at codon 10 in exon 1 of TGF-beta1 gene was associated with a severe degree of cytopenia [95% CI OR = 4.889, p = 0.0071]. These findings suggest that the investigated genetic polymorphisms do not predispose to the development of MDS, but that TGF-beta1 gene polymorphism may affect the disease progression.

Adult↗

PubMed2004

Comparison of circulating levels of interleukin-6 and tumor necrosis factor-alpha in hypertrophic cardiomyopathy and in idiopathic dilated cardiomyopathy.

It is known from the literature that the circulating levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are elevated in heart failure and idiopathic dilated cardiomyopathy (IDC). Few convincing data are available on the production of cytokines in hypertrophic cardiomyopathy (HC). The levels of circulating IL-6, the soluble form of the IL-6 receptor (sIL-6R), and TNF-alpha in 19 patients with HC, 31 patients with IDC, and 20 healthy subjects (control group) were examined and compared with their clinical parameters. The levels of TNF-alpha and circulating IL-6 proved to be elevated in the sera of patients with IDC. In contrast, the level of TNF-alpha was not elevated in HC, although the levels of IL-6 and sIL-6R were significantly higher than those in the sera of patients with IDC. Although elevated levels of IL-6 may correlate with the extent of left ventricular dysfunction in IDC, the markedly elevated IL-6 levels did not correlate with left ventricular function in HC. The markedly elevated TNF-alpha levels in IDC were associated with the elevated IL-6 levels, probably because of an inflammatory process and/or heart failure. In contrast, in HC, in which the New York Heart Association functional class was actually good, the even higher IL-6 and sIL-6R levels were not associated with a TNF-alpha elevation. In HC, the IL-6 and sIL-6R elevations were due to another mechanism, probably by way of the cardiotrophin-associated gp130 receptor. The sources of IL-6 production in HC are not clear yet.

Aged↗

PubMed2004

Effects of Helicobacter pylori infection on gastric inflammation and local cytokine production in histamine-deficient (histidine decarboxylase knock-out) mice.

UNLABELLED: Helicobacter pylori infection in humans causes gastritis. The infection elicits a complex immune response in which the activation of mast cells and histamine release is of particular importance. Histamine further promotes the immune response and stimulates gastric acid secretion. The inflammatory effects of H. pylori can be studied in intragastrically infected mice. The aim of this study was to compare the local cytokine responses of histamine-deficient, histidine decarboxylase knock-out (HDC KO) and wild-type (WT) mice following H. pylori infection. METHODS: H. pylori was administered intragastrically to HDC KO and WT mice. The animals were infected three times in a 1-week-period and were sacrificed 8 weeks after the first intervention. The local TNF-alpha, IL-6 and IL-10 cytokine levels in gastric mucosal specimens were determined by ELISA. Gastric mucosa sections were also analysed for histological signs of inflammation. To investigate the antibody response following H. pylori infection, the total anti-H. pylori IgG and the ratio of IgG1/IgG2a isotypes were determined in the serum by ELISA. RESULTS: H. pylori induced considerable cytokine production in the infected groups. The TNF-alpha and IL-6 levels were significantly higher in the WT mice than in the HDC KO mice, whereas the IL-10 levels did not differ between the groups. Anti-H. pylori IgG was detected only in the infected groups and the titre was higher in the WT mice. A higher IgG1/IgG2a ratio was observed in the H. pylori infected HDC KO group. Histological analysis revealed that the grades of inflammation were less severe in the infected HDC KO animals. CONCLUSIONS: The results suggest that H. pylori induces lower TNF-alpha and IL-6 secretion in the gastric mucosa in the HDC KO mice than in the WT animals, while the levels of induction of IL-10 were similar. The imbalance between Th1/Th2 is less pronounced in the HDC KO mice, which might explain the milder inflammation in the gastric mucosa. These results provide further information on the role of histamine in the pathomechanism of H. pylori-induced gastritis.

Animals↗

PubMed2004

Importance of cytokines, nitric oxide, and apoptosis in the pathological process of necrotizing pancreatitis in rats.

OBJECTIVES: Ischemia-reperfusion injury can be involved in the pathophysiology of acute necrotizing pancreatitis. The aim of our study was to determine the production of cytokines, tumor necrosis factor (TNF) and interleukin-6 (IL-6), the activation of the inducible nitric oxide synthase (iNOS), and the development of apoptosis during this pathologic process. METHODS: Acute pancreatitis was produced in male Wistar rats by injection of 200 microL of 6% taurocholic acid into the main pancreatic duct in combination with the temporary (15 minutes) occlusion of the inferior splenic artery. Six and 24 hours later, the histologic damage was evaluated, and serum amylase, TNF, IL-6 levels, and iNOS and apoptotic activity from pancreatic and pulmonary tissues were determined. RESULTS: Twenty-four hours after the induction of pancreatitis, the mortality rate was 63%. During this period, the serum TNF and IL-6 levels were permanently high (50 +/- 12 and 58 +/- 10 U/mL and 7083 +/- 1610 and 6790 +/- 850 U/mL after 6 and 24 hours, respectively). The iNOS activity showed an increasing tendency in the pancreas, and a decrease following an initial increase in the lung (from 4.2 +/- 0.6 to 5 +/- 0.4 and from 6.8 +/- 0.6 to 3.8 +/- 0.5 pmol/min/mg protein after 6 and 24 hours, respectively). Histologic examination confirmed severe necrotizing pancreatitis. In the pancreas, the apoptotic activity increased significantly (from 4 +/- 4 to 27 +/- 5/mm at 6 and 24 hours), while in the lungs, following an initial increase it declined during the course of necrotizing pancreatitis (from 49 +/- 4 to 11 +/- 6/mm at 6 and 24 hours). CONCLUSION: Our results indicate that intraductal taurocholic acid and ischemia-reperfusion provokes severe acute necrotizing pancreatitis with a high mortality rate and leads to systemic inflammatory reaction, which appears to be the consequence of the activation of the cytokine cascade and iNOS. The degree of NO overproduction by iNOS corresponds with the apoptotic process in the pancreas and the lung.

Animals↗

PubMed2004

Investigation of the prognostic value of TNF-alpha gene polymorphism among patients treated with infliximab, and the effects of infliximab therapy on TNF-alpha production and apoptosis.

OBJECTIVES: Infliximab, a chimeric anti-tumor necrosis factor (TNF) antibody, is highly effective for the treatment of Crohn's disease (CD) and rheumatoid arthritis (RA). Our experiments focused on RA and CD patients receiving infliximab. Since cytokine production is largely determined by genetic factors, the promoter polymorphisms of TNF-alpha were examined among these patients. Additionally, the changes caused by infliximab in the TNF-alpha-producing ability and apoptosis of peripheral blood mononuclear cells (PBMCs) were investigated. METHODS: The TNF-alpha genotypes were analyzed by PCR-RFLP. The in vitro TNF-alpha production of the PBMCs was detected by flow cytometric analysis. The TNF-alpha concentration in the supernatant was measured by bioassay. Apoptosis was detected by annexin V-fluorescein isothiocyanate labeling. RESULTS AND CONCLUSIONS: 8 of the 12 nonresponder patients carried the TNF A allele associated with high TNF-alpha production. We suggest that the determination of TNF polymorphism may help identify more suitable candidates for infliximab treatment. Although in vitro infliximab treatment for 48 h resulted in significant (44.2 +/- 1.17%) apoptosis in PBMCs, in ex vivo samples from RA patients who received infliximab, apoptosis was only 13.3 +/- 1.6%. Furthermore, infliximab did not result in irreversible inhibition of the TNF-alpha-producing ability or in the significant apoptosis of PBMCs.

Alleles↗

PubMed2004

Bacterial models for tumor development. Mini-review.

UNLABELLED: The tumor-inducing effects of Agrobacterium, Bartonella and Helicobacter bacterial species are compared step by step. An analogy for the existence of these individual steps is considered in connection with the development of cancer. The transformations of eukaryotic cells occur in particular in the type IV secretion system, i.e. involving the simultaneous transmission of DNA and protein from bacterial cells to eukaryotic cells. Thus, transfected cells facilitate the indefinite growth of tissue cells and additionally produce growth factors, triggering further bacterial multiplication. The higher numbers of bacteria then produce more transfection and the cycle repeats as long as the host lives. The main limiting factor is the frequency of bacterial infection, while the secondary rate-limiting factors are the levels of transforming growth factors and factors triggering bacteria growth. CONCLUSIONS: Analogous processes are probably responsible for the tumor induction by the three different bacterial species; however, the critical points for eradication are different. The early eradication or limitation of B. henselae or H. pylori can prevent hemangiomas, stomach cancer and malignant cell proliferation. The crown gall formation by A. tumefaciens can only be avoided by prevention of the transforming activity of a single bacterial infection. Questions arise as to what is common in the three processes, and the nature of the rate-limiting step in the three different models. The frequency of transformation is the rate-limiting step, but the co-transmission of the DNA-protein complex is common in the three systems.

Agrobacterium tumefaciens↗

PubMed2004

Infectious plasmid resistance and efflux pump mediated resistance.

Various bacterial plasmids can be eliminated from bacterial species cultured as pure or mixed bacterial cultures by non-mutagenic heterocyclic compounds at subinhibitory concentrations. For plasmid curing, the replication should be inhibited at three different levels simultaneously: the intracellular replication of plasmid DNA, partition and intercellular transconjugal transfer. The antiplasmid action of the compounds depends on the chemical structure. The targets for antiplasmid compounds were analysed in detail. It was found that amplified extrachromosomal DNA in the superhelical state binds more drug molecules than does the linear or open-circular form of the plasmid or the chromosome, without stereospecificity which leads to functional inactivation of the extrachromosomal genetic code. Plasmid elimination also occurs in ecosystems containing numerous bacterial species simultaneously, but the elimination of antibiotic resistance-encoding plasmids from all individual cells of the population is never complete. The medical significance of plasmid elimination in vitro is, it provides a method to isolate plasmid-free bacteria for biotechnology without any risk of mutations, and it opens up a new perspective in rational drug design against bacterial plasmids. Hypothetically, the combination of antiplasmid drugs and antibiotics may improve the effectivity of antibiotics against resistant bacteria; therefore, the results cannot be exploited until the curing efficiency reaches 100%. Inhibition of the conjugational transfer of antibiotic resistance plasmids can be exploited to reduce the spreading of these plasmids in ecosystems.

Anti-Bacterial Agents↗

PubMed2004

The antimotility action of a trifluoromethyl ketone on some gram-negative bacteria.

The inhibition of bacterial motility was studied by a trifluoro methyl ketone derivative on two Escherichia coli strains (wild strain having a proton pump system and the proton pump-deficient mutant strain) and two Helicobacter pylori strains (clarithromycin susceptible and clarithromycin resistant). Evidence is presented of the inhibitory action of 1-(2-benzoxazolyl)-3,3,3-trifluoro-2-propanone (TF18) on the proton motive forces of the two bacterial strains by affecting the action of biological motor and proton efflux in the membranes. The swimming, the forward motion was more sensitive than the vibration or tumbling to the inhibition. We suppose that the inhibiton of bacterial motility is related to the virulence of bacteria: consequently the pathogenicity can be reduced in the presence of TF18.

Anti-Infective Agents↗

PubMed2004

Different staphylococcal strains elicit different levels of production of T-helper 1-inducing cytokines.

Cytokine production has been implicated in the pathogenic mechanisms of infections caused by the staphylococci, since these bacteria may act as strong cytokine inducers. To gain deeper insight into the Th1 immune response activated by these bacteria, we have analyzed the interferon (IFN), interleukin-12 (IL-12) and IL-18-inducing activities of different Staphylococcus aureus (S. aureus), S. epidermidis and S. saprophyticus strains in human monocytes and murine bone marrow macrophages. A large majority of the S. aureus strains elicited the simultaneous production of IL-12 p70 and IFN-alpha in the human monocytes, while the S. epidermidis and S. saprophyticus strains induced only a low level of production, if any, of these cytokines. Furthermore, a majority of the S. aureus strains induced significantly higher IL-12 p70 and IL-18 titers in the murine bone marrow macrophages than did the S. epidermidis and S. saprophyticus strains. As IL-12, IL-18 and IFN-alpha stimulate Th1 differentiation synergistically, we suggest that S. aureus strains bias the immune response toward a Th1 phenotype, whereas S. epidermidis and S. saprophyticus strains provide a weaker stimulus for the production of Th1-inducing cytokines, and accordingly possibly elicit a less extensive Th1-associated adaptive immunity.

Animals↗

PubMed2004

Tumour necrosis factor-alpha and heat-shock protein 70-2 gene polymorphisms in a family with rheumatoid arthritis.

OBJECTIVES: The aim of this work was to investigate the prevalence of TNF-alpha-308 polymorphism among the 29 members of a family with RA and the association between the MHC-linked biallelic HSP70-2 gene and the TNF-alpha polymorphism. Five of the members with RA were diagnosed by using the revised 1987 ACR criteria, and 1 member suffered from SLE. METHODS: The variations in the TNF-alpha and the HSP70-2 genotypes were analyzed by PCR-RFLP, using NcoI and PstI restriction enzymes. RESULTS: Two of the 29 members were homozygotes for allele A, 18 were heterozygotes (TNF A/G) and 9 of them were homozygotes for allele G. Nineteen of the 29 were heterozygotes for HSP70-2 (A/G), 10 of them were homozygotes for the G allele, and none were homozygotes for allele A. Four of the 5 the RA patients carried the A allele for TNF-alpha all 5 were heterozygotes for HSP70-2 genotypes. CONCLUSION: The carriage of the A allele for TNF-alpha of -308 SNP in 4 of the 5 RA patients, and the high prevalence (68.0%) of TNF A allele carriers in this family confirms the important role of this candidate gene in the pathomechanism of RA, and might be of prognostic value for future clinical observations. Further, to test for association a much larger set of genetically independent patients and controls is needed.

Alleles↗

PubMed2004

Helicobacter pylori-induced immunological responses in patients with duodenal ulcer and in patients with cardiomyopathies.

The interaction between the bacteria and the host is a key factor determining the clinical consequences of H. pylori infection. The immune system plays an important role in either promoting or preventing the disease. The mucosal production of TNF-alpha, IL-6, IL-8 and IL-10 and the CagA status were investigated in H. pylori-positive patients with duodenal ulcer (DU). The concentrations of these cytokines in gastric antral mucosal specimens from patients infected with H. pylori (n = 40) were determined by ELISA and compared with data on mucosal specimens from H. pylori-negative patients (n = 12). The local TNF-alpha, IL-6 and IL-8 concentrations in the antral biopsy samples were significantly higher (p < 0.001) in the patients infected with H. pylori than in the samples from the H. pylori-negative subjects. CagA positivity was demonstrated in 39 (97.5%) of the 40 patients with DU, and in 41 (70.7%) of H. pylori-positive (58 of 100) healthy blood donors. In complementary studies focusing on extragastric disease, it was found that 57% of patients with ischaemic heart disease were seropositive as concerns H. pylori, and 91% of them had antibodies against human heat shock protein 60, too. This study suggests that, besides the bacterial virulence factor, the host response of an increased mucosal production of inflammatory cytokines can be relevant to the gastric pathophysiology in H. pylori-induced DU. At the same time, in ischaemic heart diseases the role of autoimmune processes induced by H. pylori cannot be excluded.

Antigens, Bacterial↗

PubMed2003

NF-kappaB activation is detrimental in arginine-induced acute pancreatitis.

The transcription factor nuclear factor kappaB (NF-kappaB) has been shown to have a critical role in the pathogenesis of sodium taurocholate- and cerulein-induced acute pancreatitis by regulating the expression of many proinflammatory genes in the pancreas. Heat shock proteins (HSPs), on the other hand, protect the pancreas against cellular damage. The aims of the present study were: (i) to investigate pancreatic NF-kappaB activation, proinflammatory cytokine synthesis, and cytoprotective HSP induction during L-arginine- (Arg-) induced acute pancreatitis in rats, and (ii) to establish whether pretreatment with pyrrolidine dithiocarbamate (PDTC) or methylprednisolone (MP) can block the activation of pancreatic NF-kappaB and determine their effects on the severity of Arg-induced acute pancreatitis. The dose-response (3 or 4 g/kg) and time-effect (0.5-96 h) curves relating to the action of Arg on pancreatic NF-kappaB activation and IL-1beta, TNF-alpha, HSP60, and HSP72 synthesis were evaluated. Various doses of PDTC or MP were administered 1 h before the induction of pancreatitis. We demonstrated that Arg specifically and dose-dependently induces pancreatitis, activates NF-kappaB (only the 3 g/kg dose) and proinflammatory cytokine synthesis, and increases the expressions of HSP60 and HSP72 in the pancreas of rats. The lower dose of Arg induced a less severe pancreatitis, but larger increases in the levels of HSPs. The present work supports and extends earlier observations that NF-kappaB activation is a common mechanism in acute pancreatitis, although it is dose dependent and occurs at a later stage in Arg-induced pancreatitis as compared with other models. PDTC and MP pretreatment dose-dependently blocked NF-kappaB activation and proinflammatory cytokine expression and ameliorated many of the examined laboratory (the pancreatic weight/body weight ratio, the pancreatic myeloperoxidase activity, the pancreatic contents of protein, amylase and trypsinogen, the degrees of lipid peroxidation and protein oxidation, and the nonprotein sulfhydryl group content) and morphological parameters of the disease. These findings suggest that pretreatment with PDTC or MP has an anti-inflammatory effect during Arg-induced pancreatitis, which is at least partly mediated by the inhibition of NF-kappaB activation and proinflammatory cytokine synthesis. The increased levels of HSPs most probably act to limit the severity of the disease.

Acute Disease↗