Over 50% of the world population is chronically infected by the gastric pathogen, Helicobacter py... more Over 50% of the world population is chronically infected by the gastric pathogen, Helicobacter pylori, which is responsible for most peptic ulcer disease and is closely associated with adenocarcinoma of the stomach. Current therapies for peptic ulcer disease include antibiotic eradication of H. pylori infection. While effective, the high cost, difficulty of patient compliance with the treatment regimens, and risks of selection for resistant strains make these therapies impractical on a large scale. Studies of the pathogenesis of H. pylori have led to the identification of bacterial antigens as candidates for inclusion in novel vaccines against this disease. Both prophylactic \U1d therapeutic vaccination have been demonstrated in animal models of Helicobacter infection. Preclinical evaluations of several antigens are at present under way and trials of vaccination in humans are planned.
30 Lf/ml, respectively) and B. pertussis bacterial cells (25opacimetric units per ml) inactivated... more 30 Lf/ml, respectively) and B. pertussis bacterial cells (25opacimetric units per ml) inactivated either with formalinalone (DPT WTF) or with both heat and formalin (DPTWTFC).All the cellular vaccines (either wild type [WT] ormutant)contained0.6mgofaluminiumphosphate(A1-P) perml as adjuvant. All cellular vaccines contained approxi-mately 50,000 endotoxin units per ml, while DPT PFKcontainedonly91endotoxinunitspermlasmeasuredbytheLimulusamoebocytelysate assay. Wethus usedan amountofB.
The effective adjuvant activity of bacteria and bacterial products relies upon their ability to s... more The effective adjuvant activity of bacteria and bacterial products relies upon their ability to stimulate the reticuloendothelial system, thus enhancing
HE GROWTH OF an organ or a cell population is de- pendent on an imbalanced ratio of cell births t... more HE GROWTH OF an organ or a cell population is de- pendent on an imbalanced ratio of cell births to cell deaths. Apoptosis, a physiologic, active mode of cell death,' is recognized as a normal developmental event that is critical for organogenesis in a wide variety of contexts and is often more relevant than mitosis.' Moreover, it has been demon-
Infection of the gastroduodenal mucosa by the gram-negative organism Helicobacter pylori is assoc... more Infection of the gastroduodenal mucosa by the gram-negative organism Helicobacter pylori is associated with the occurrence of chronic active gastritis and peptic ulcer, and also increases the risk of gastric cancer (Parsonnet et al. 1991, 1994; Blaser and Parsonnet 1994). The risk of infection is high in childhood and is directly correlated to low hygienic conditions and overcrowded environments (Webb et al. 1994). Once established, a successful colonization may be lifelong. Due to significant improvement in hygienic conditions the risk of exposure to infection is now decreasing in the developed countries, where the prevalence of infection approximately increases 1% per year of age and is about 40%–50% in the over-50-year-old population. However, in developing countries as much as 80% of the young population can be infected before adolescence, and nearly all elderly individuals are infected (Megraud 1994).
Chronic infection of the gastric mucosa by the Gram negative organism Helicobacter pylori causes ... more Chronic infection of the gastric mucosa by the Gram negative organism Helicobacter pylori causes chronic active gastritis, peptic ulcer and increases the risk of gastric cancer (Parsonnet et al., 1991; Parsonnet et al., 1994; Blaser and Parsonnet, 1994). The risk of infection is high in childhood and is directly correlated to hygienic conditions and overcrowded homes (Webb et al., 1994). Once established, a successful colonization may be lifelong. Due to significant improvement in hygienic conditions the risk of exposure to infection is now decreasing in the developed contries, where the prevalence of infection approximately increases 1% per year of age and is about 40–50% in the over 50 year old population. However as high as 80% of the young population can be infected in developing countries before the adolescence, and nearly all elderly individuals are infected (Megraud, 1994).
Publisher Summary This chapter describes the technical aspects of mouse model of Helicobacter pyl... more Publisher Summary This chapter describes the technical aspects of mouse model of Helicobacter pylori infection model and critically reviews its usefulness in the development of new strategies against this important human pathogen. Several mouse strains can be used for this animal model. For this model, the mice are housed in a negative-pressure air-conditioned BL2 animal facility that allows a safe experimentation with pathogens like H. pylori and ensures that no contamination from the external environment may occur. They are housed on a 12-hour light-dark schedule and have ad-libitum access to autoclave-sterilized standard diet pellets and to filter-sterilized water. The bacteria to be inoculated into mice are grown on agar plates, which are incubated in microaerophilic conditions. Bacteria cultured either in liquid conditions or on agar plates incubated with 5% CO 2 instead of the microaerophilia fail to significantly colonize the mice. The bacteria recovered from one well-grown plate are usually sufficient to inoculate 10–15 mice. The pathological changes induced by infection are followed by histological examination. At 8 weeks after infection, gastric lesions consist mainly of focal epithelial damage. Fields showing superficial epithelial erosive-reparative lesions with polymorphonuclear leukocytes infiltrating the lesions and the surrounding mucosa are present in most of the infected mice. This is presently the only model that allows to test the potential, as vaccine candidates, of virulence factors that are peculiar to the more virulent (type I) H. pylori strains, such as VacA and those expressed by the cag pathogenicity island (PAl). This model has also been used for the rapid in-vivo screening of various anti-H, pylori chemotherapeutics that are under development.
Helicobacter pylori causes gastroduodenal ulcer disease in humans. T lymphocytes and their cytoki... more Helicobacter pylori causes gastroduodenal ulcer disease in humans. T lymphocytes and their cytokines are thought to play a substantial role in the control of H. pylori infection. To determine the importance of T helper (Th) cytokines and background genes we investigated the natural course of H. pylori infection in BALB/c and C57BL/6 wild-type or mutant mice deficient for either interleukin (IL)-4 or interferon (IFN)-gamma. H. pylori SPM 326 persisted for at least six months in C57BL/6 but was cleared by BALB/c wild-type mice nine weeks postinfection. H. pylori was recovered more frequently from IFN-gamma(-/-) BALB/c and IFN-gamma( -/-) C57BL/6 mice than from the respective wild-type animals. In contrast, IL-4 deficiency had no detectable effect on H. pylori recovery rates from either strain of mice. Our data suggest a protective role of IFN-gamma by mediating inflammation in murine H. pylori infection. In addition, our data emphasize that background genes which differ between BALB/c and C57BL/6 mice regulate the clearance of H. pylori.
The pathogenic role ofHelicobacter pylorivirulence factors has been studied with a mouse model of... more The pathogenic role ofHelicobacter pylorivirulence factors has been studied with a mouse model of gastric disease. BALB/c mice were treated orally with different amounts of sonic extracts of cytotoxicH. pyloristrains (NCTC 11637, 60190, 84-183, and 87A300 (CagA 1 /Tox 1 )). The pathological effects on histological sections of gastric mucosae were assessed and were compared with the effects of treatments
The human pathogen Helicobacter pylori is associated with gastritis, peptic ulcer disease, and ga... more The human pathogen Helicobacter pylori is associated with gastritis, peptic ulcer disease, and gastric cancer. The pathogenesis of H. pylori infection in vivo was studied by adapting fresh clinical isolates of bacteria to colonize the stomachs of mice. A gastric pathology resembling human disease was observed in infections with cytotoxin-producing strains but not with noncytotoxic strains. Oral immunization with purified H. pylori antigens protected mice from bacterial infection. This mouse model will allow the development of therapeutic agents and vaccines against H. pylori infection in humans.
Interleukin-1 /3 (IL-1 B) has been shown to specifically increase the release of prostaglandin (P... more Interleukin-1 /3 (IL-1 B) has been shown to specifically increase the release of prostaglandin (PG) E, from rat hypothalamic explants in short-term experiments. In this study we attempted to characterize the receptor subtype(s) involved in this response. Rat hypothalamic explants were incubated with mouse monoclonal antibodies (mAbs) raised against human ILl type I or type II receptors, IL-1 receptor antagonist (IL-lra) and a-mclanocyte-stimulating hormone (a-MSH) (which appears to antagonize certain IL-1 induced inflammatory effects in viva), alone and in :the presence of IL-l@ PGE, released into the incubation medium was measured by radioimmunoassay. The anti-type I mAb reduced both basal and IL-1 @-stimulated PGE, release at 10 Fg/ml, but not at lower concentrations. The anti-type II mAb also produced a significant decrease in stimulated release but had no effect on basal release. IL-lra mimicked the effects of the anti-type I mAb, while ru-MSH failed to alter either basal or stimulated PGE, release. These findings suggest that IL-1 p controls production and release of PGE, by the rat hypothalamus via both type 1 and type II receptors, although the latter appear to be involved only in the response to high levels of ILl .
Progress in elucidating the pathogenesis of Helicobacter pylori gastric infection and in developi... more Progress in elucidating the pathogenesis of Helicobacter pylori gastric infection and in developing an H. pylori vaccine will be aided by an animal model in which H. pylori can be reliably detected. To validate the use of the mouse model of H. pylori infection, we determined the susceptibility of three inbred strains of mice (C57BL / 6J, C57BL / 10J and BALB / c) to two VacA1 / CagA1 isolates of H. pylori (SPM326 and M1.16) and determined the effectiveness of microbiological, histological and molecular assays for H. pylori detection. For the detection of H. pylori in inoculated mice, reverse transcriptase-polymerase chain reaction was the most sensitive assay (82%), histological evaluation the next most sensitive (66%) and microbiological evaluation the least sensitive (38%); the assays were equally specific (100%). Of the two H. pylori isolates, M1.16 showed the highest rate of colonization, but SPM326 displayed the highest rate of persistent infection. Among the three mouse strains, C57BL / 6J mice showed the highest level of both susceptibility to colonization and persistent infection. Anti-H. pylori antibody responses were induced in all inoculated mice and persisted for up to 8 weeks after H. pylori clearance. These results indicate that inbred mice experimentally infected with H. pylori is a reliable model for human infection, but host susceptibility to colonization and persistence of infection are dependent on the H. pylori isolate and the mouse strain.
Helicobacter pylori is a major risk factor for peptic ulcer, but studies on the role of H. pylori... more Helicobacter pylori is a major risk factor for peptic ulcer, but studies on the role of H. pylori infection in gastric pathology are limited due to lack of convenient models resembling H. pylori infection in humans. We studied the effects of inoculation of conventional BALB/c mice with a toxigenic (cytotoxin associated gene A (cagA)+ and vacuolating cytotoxin gene A (vacA+) H. pylori strain on the course of healing of gastric ulcers. Following inoculation of toxigenic H. pylori or vehicle, gastric ulcers were produced in mice, which were then killed either at day 0 or after 2, 4, 7, 14 or 28 days and ulcer area and gastric blood flow (GBF) were determined. Gastric secretions from mice with chronic gastric fistulae were studied before and after inoculation with toxigenic H. pylori or vehicle (saline). The area (7 mm2 ) of ulcers in control mice decreased gradually and disappeared almost completely after 14 or 28 days. The ulcers in H. pylori-infected mice were present at all test days, showing a larger area than in vehicle control animals. The GBF in control mice rose gradually with decreasing ulcer size, being significantly higher at the ulcer margin than the ulcer crater. In contrast, the GBF in H. pylori-infected mice was significantly lower at the ulcer area than that in the vehicle controls but, again, the GBF at the ulcer margin was always higher than at the ulcer crater. Gastric acid output was reduced by more than 50% immediately after H. pylori inoculation and was accompanied by a significant increase in plasma gastrin release and a fall in gastric luminal somatostatin content. These secretory changes persisted at all test days. Oedema/congestion of surface epithelium appeared after 7 days and mucosal inflammatory infiltration appeared after 14 days, to further increase after 28 days, upon the induction of ulcer. Plasma interleukin (IL)-Iß and IL-12 were significantly elevated above the initial values compared with controls. Conventional mice with gastric ulcers can be successfully infected with an H. pylori strain expressing cagA and vacA cytotoxin and this infection markedly delays healing of the ulcers, probably due to the fall in GBF in the ulcer area, mucosal inflammation, cytokine release and impairment of the gastrin-somatostatin link.
Helicobacter pylori infection results in chronic gastritis, which is initiated by the release of ... more Helicobacter pylori infection results in chronic gastritis, which is initiated by the release of cytokines like interleukin (IL)-12 and IL-8 from mononuclear cells, and IL-8 from gastric epithelial cells. The severity of gastritis is influenced both by host factors and by bacterial factors such as the Cag proteins and the vacuolating cytotoxin VacA. Amounts of IL-12 and IL-8 produced by monocytic THP-1 cells differed considerably between the eight H. pylori isolates tested, but in contrast to H. pylori-induced IL-8 production by gastric epithelial cells, did not correlate to the Cag and VacA types of the strains. Apparently, in addition to Cag and VacA, other bacterial factors determine the extent in which H. pylori induced IL production in monocytes. ß 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Microbiological Societies.
Over 50% of the world population is chronically infected by the gastric pathogen, Helicobacter py... more Over 50% of the world population is chronically infected by the gastric pathogen, Helicobacter pylori, which is responsible for most peptic ulcer disease and is closely associated with adenocarcinoma of the stomach. Current therapies for peptic ulcer disease include antibiotic eradication of H. pylori infection. While effective, the high cost, difficulty of patient compliance with the treatment regimens, and risks of selection for resistant strains make these therapies impractical on a large scale. Studies of the pathogenesis of H. pylori have led to the identification of bacterial antigens as candidates for inclusion in novel vaccines against this disease. Both prophylactic \U1d therapeutic vaccination have been demonstrated in animal models of Helicobacter infection. Preclinical evaluations of several antigens are at present under way and trials of vaccination in humans are planned.
30 Lf/ml, respectively) and B. pertussis bacterial cells (25opacimetric units per ml) inactivated... more 30 Lf/ml, respectively) and B. pertussis bacterial cells (25opacimetric units per ml) inactivated either with formalinalone (DPT WTF) or with both heat and formalin (DPTWTFC).All the cellular vaccines (either wild type [WT] ormutant)contained0.6mgofaluminiumphosphate(A1-P) perml as adjuvant. All cellular vaccines contained approxi-mately 50,000 endotoxin units per ml, while DPT PFKcontainedonly91endotoxinunitspermlasmeasuredbytheLimulusamoebocytelysate assay. Wethus usedan amountofB.
The effective adjuvant activity of bacteria and bacterial products relies upon their ability to s... more The effective adjuvant activity of bacteria and bacterial products relies upon their ability to stimulate the reticuloendothelial system, thus enhancing
HE GROWTH OF an organ or a cell population is de- pendent on an imbalanced ratio of cell births t... more HE GROWTH OF an organ or a cell population is de- pendent on an imbalanced ratio of cell births to cell deaths. Apoptosis, a physiologic, active mode of cell death,' is recognized as a normal developmental event that is critical for organogenesis in a wide variety of contexts and is often more relevant than mitosis.' Moreover, it has been demon-
Infection of the gastroduodenal mucosa by the gram-negative organism Helicobacter pylori is assoc... more Infection of the gastroduodenal mucosa by the gram-negative organism Helicobacter pylori is associated with the occurrence of chronic active gastritis and peptic ulcer, and also increases the risk of gastric cancer (Parsonnet et al. 1991, 1994; Blaser and Parsonnet 1994). The risk of infection is high in childhood and is directly correlated to low hygienic conditions and overcrowded environments (Webb et al. 1994). Once established, a successful colonization may be lifelong. Due to significant improvement in hygienic conditions the risk of exposure to infection is now decreasing in the developed countries, where the prevalence of infection approximately increases 1% per year of age and is about 40%–50% in the over-50-year-old population. However, in developing countries as much as 80% of the young population can be infected before adolescence, and nearly all elderly individuals are infected (Megraud 1994).
Chronic infection of the gastric mucosa by the Gram negative organism Helicobacter pylori causes ... more Chronic infection of the gastric mucosa by the Gram negative organism Helicobacter pylori causes chronic active gastritis, peptic ulcer and increases the risk of gastric cancer (Parsonnet et al., 1991; Parsonnet et al., 1994; Blaser and Parsonnet, 1994). The risk of infection is high in childhood and is directly correlated to hygienic conditions and overcrowded homes (Webb et al., 1994). Once established, a successful colonization may be lifelong. Due to significant improvement in hygienic conditions the risk of exposure to infection is now decreasing in the developed contries, where the prevalence of infection approximately increases 1% per year of age and is about 40–50% in the over 50 year old population. However as high as 80% of the young population can be infected in developing countries before the adolescence, and nearly all elderly individuals are infected (Megraud, 1994).
Publisher Summary This chapter describes the technical aspects of mouse model of Helicobacter pyl... more Publisher Summary This chapter describes the technical aspects of mouse model of Helicobacter pylori infection model and critically reviews its usefulness in the development of new strategies against this important human pathogen. Several mouse strains can be used for this animal model. For this model, the mice are housed in a negative-pressure air-conditioned BL2 animal facility that allows a safe experimentation with pathogens like H. pylori and ensures that no contamination from the external environment may occur. They are housed on a 12-hour light-dark schedule and have ad-libitum access to autoclave-sterilized standard diet pellets and to filter-sterilized water. The bacteria to be inoculated into mice are grown on agar plates, which are incubated in microaerophilic conditions. Bacteria cultured either in liquid conditions or on agar plates incubated with 5% CO 2 instead of the microaerophilia fail to significantly colonize the mice. The bacteria recovered from one well-grown plate are usually sufficient to inoculate 10–15 mice. The pathological changes induced by infection are followed by histological examination. At 8 weeks after infection, gastric lesions consist mainly of focal epithelial damage. Fields showing superficial epithelial erosive-reparative lesions with polymorphonuclear leukocytes infiltrating the lesions and the surrounding mucosa are present in most of the infected mice. This is presently the only model that allows to test the potential, as vaccine candidates, of virulence factors that are peculiar to the more virulent (type I) H. pylori strains, such as VacA and those expressed by the cag pathogenicity island (PAl). This model has also been used for the rapid in-vivo screening of various anti-H, pylori chemotherapeutics that are under development.
Helicobacter pylori causes gastroduodenal ulcer disease in humans. T lymphocytes and their cytoki... more Helicobacter pylori causes gastroduodenal ulcer disease in humans. T lymphocytes and their cytokines are thought to play a substantial role in the control of H. pylori infection. To determine the importance of T helper (Th) cytokines and background genes we investigated the natural course of H. pylori infection in BALB/c and C57BL/6 wild-type or mutant mice deficient for either interleukin (IL)-4 or interferon (IFN)-gamma. H. pylori SPM 326 persisted for at least six months in C57BL/6 but was cleared by BALB/c wild-type mice nine weeks postinfection. H. pylori was recovered more frequently from IFN-gamma(-/-) BALB/c and IFN-gamma( -/-) C57BL/6 mice than from the respective wild-type animals. In contrast, IL-4 deficiency had no detectable effect on H. pylori recovery rates from either strain of mice. Our data suggest a protective role of IFN-gamma by mediating inflammation in murine H. pylori infection. In addition, our data emphasize that background genes which differ between BALB/c and C57BL/6 mice regulate the clearance of H. pylori.
The pathogenic role ofHelicobacter pylorivirulence factors has been studied with a mouse model of... more The pathogenic role ofHelicobacter pylorivirulence factors has been studied with a mouse model of gastric disease. BALB/c mice were treated orally with different amounts of sonic extracts of cytotoxicH. pyloristrains (NCTC 11637, 60190, 84-183, and 87A300 (CagA 1 /Tox 1 )). The pathological effects on histological sections of gastric mucosae were assessed and were compared with the effects of treatments
The human pathogen Helicobacter pylori is associated with gastritis, peptic ulcer disease, and ga... more The human pathogen Helicobacter pylori is associated with gastritis, peptic ulcer disease, and gastric cancer. The pathogenesis of H. pylori infection in vivo was studied by adapting fresh clinical isolates of bacteria to colonize the stomachs of mice. A gastric pathology resembling human disease was observed in infections with cytotoxin-producing strains but not with noncytotoxic strains. Oral immunization with purified H. pylori antigens protected mice from bacterial infection. This mouse model will allow the development of therapeutic agents and vaccines against H. pylori infection in humans.
Interleukin-1 /3 (IL-1 B) has been shown to specifically increase the release of prostaglandin (P... more Interleukin-1 /3 (IL-1 B) has been shown to specifically increase the release of prostaglandin (PG) E, from rat hypothalamic explants in short-term experiments. In this study we attempted to characterize the receptor subtype(s) involved in this response. Rat hypothalamic explants were incubated with mouse monoclonal antibodies (mAbs) raised against human ILl type I or type II receptors, IL-1 receptor antagonist (IL-lra) and a-mclanocyte-stimulating hormone (a-MSH) (which appears to antagonize certain IL-1 induced inflammatory effects in viva), alone and in :the presence of IL-l@ PGE, released into the incubation medium was measured by radioimmunoassay. The anti-type I mAb reduced both basal and IL-1 @-stimulated PGE, release at 10 Fg/ml, but not at lower concentrations. The anti-type II mAb also produced a significant decrease in stimulated release but had no effect on basal release. IL-lra mimicked the effects of the anti-type I mAb, while ru-MSH failed to alter either basal or stimulated PGE, release. These findings suggest that IL-1 p controls production and release of PGE, by the rat hypothalamus via both type 1 and type II receptors, although the latter appear to be involved only in the response to high levels of ILl .
Progress in elucidating the pathogenesis of Helicobacter pylori gastric infection and in developi... more Progress in elucidating the pathogenesis of Helicobacter pylori gastric infection and in developing an H. pylori vaccine will be aided by an animal model in which H. pylori can be reliably detected. To validate the use of the mouse model of H. pylori infection, we determined the susceptibility of three inbred strains of mice (C57BL / 6J, C57BL / 10J and BALB / c) to two VacA1 / CagA1 isolates of H. pylori (SPM326 and M1.16) and determined the effectiveness of microbiological, histological and molecular assays for H. pylori detection. For the detection of H. pylori in inoculated mice, reverse transcriptase-polymerase chain reaction was the most sensitive assay (82%), histological evaluation the next most sensitive (66%) and microbiological evaluation the least sensitive (38%); the assays were equally specific (100%). Of the two H. pylori isolates, M1.16 showed the highest rate of colonization, but SPM326 displayed the highest rate of persistent infection. Among the three mouse strains, C57BL / 6J mice showed the highest level of both susceptibility to colonization and persistent infection. Anti-H. pylori antibody responses were induced in all inoculated mice and persisted for up to 8 weeks after H. pylori clearance. These results indicate that inbred mice experimentally infected with H. pylori is a reliable model for human infection, but host susceptibility to colonization and persistence of infection are dependent on the H. pylori isolate and the mouse strain.
Helicobacter pylori is a major risk factor for peptic ulcer, but studies on the role of H. pylori... more Helicobacter pylori is a major risk factor for peptic ulcer, but studies on the role of H. pylori infection in gastric pathology are limited due to lack of convenient models resembling H. pylori infection in humans. We studied the effects of inoculation of conventional BALB/c mice with a toxigenic (cytotoxin associated gene A (cagA)+ and vacuolating cytotoxin gene A (vacA+) H. pylori strain on the course of healing of gastric ulcers. Following inoculation of toxigenic H. pylori or vehicle, gastric ulcers were produced in mice, which were then killed either at day 0 or after 2, 4, 7, 14 or 28 days and ulcer area and gastric blood flow (GBF) were determined. Gastric secretions from mice with chronic gastric fistulae were studied before and after inoculation with toxigenic H. pylori or vehicle (saline). The area (7 mm2 ) of ulcers in control mice decreased gradually and disappeared almost completely after 14 or 28 days. The ulcers in H. pylori-infected mice were present at all test days, showing a larger area than in vehicle control animals. The GBF in control mice rose gradually with decreasing ulcer size, being significantly higher at the ulcer margin than the ulcer crater. In contrast, the GBF in H. pylori-infected mice was significantly lower at the ulcer area than that in the vehicle controls but, again, the GBF at the ulcer margin was always higher than at the ulcer crater. Gastric acid output was reduced by more than 50% immediately after H. pylori inoculation and was accompanied by a significant increase in plasma gastrin release and a fall in gastric luminal somatostatin content. These secretory changes persisted at all test days. Oedema/congestion of surface epithelium appeared after 7 days and mucosal inflammatory infiltration appeared after 14 days, to further increase after 28 days, upon the induction of ulcer. Plasma interleukin (IL)-Iß and IL-12 were significantly elevated above the initial values compared with controls. Conventional mice with gastric ulcers can be successfully infected with an H. pylori strain expressing cagA and vacA cytotoxin and this infection markedly delays healing of the ulcers, probably due to the fall in GBF in the ulcer area, mucosal inflammation, cytokine release and impairment of the gastrin-somatostatin link.
Helicobacter pylori infection results in chronic gastritis, which is initiated by the release of ... more Helicobacter pylori infection results in chronic gastritis, which is initiated by the release of cytokines like interleukin (IL)-12 and IL-8 from mononuclear cells, and IL-8 from gastric epithelial cells. The severity of gastritis is influenced both by host factors and by bacterial factors such as the Cag proteins and the vacuolating cytotoxin VacA. Amounts of IL-12 and IL-8 produced by monocytic THP-1 cells differed considerably between the eight H. pylori isolates tested, but in contrast to H. pylori-induced IL-8 production by gastric epithelial cells, did not correlate to the Cag and VacA types of the strains. Apparently, in addition to Cag and VacA, other bacterial factors determine the extent in which H. pylori induced IL production in monocytes. ß 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Microbiological Societies.
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