Infection of the gastric antrum byHelicobacter pyloni is characterised by a cellular inflammatory infiltrate. Whether cytokines are involved in the pathogenesis of this gastritis has been investigated by studying the effect of eradicating Hpylori on the expression of genes encoding the cytokines interleukin 8 (IL-8) and tumour necrosis factor ot (TNF-ot) in the antral mucosa. Gastric antral biopsy specimens were taken from nine patients with duodenal ulcers and cytokine transcripts were identified and quantified by northern blotting. After H pylorn had been eradicated the chronic inflammatory infiltrate decreased in all the patients and the polymorphonuclear infiltrate virtually disappeared. Expression of genes also decreased. After eradication, the median TNF-a mRNA/rRNA fell to 48% (p=002) and the median IL-8 mRNA/rRNA fell to 5Ol (p=0004) of initial values. These results support the role of increased synthesis of these cytokines in the pathogenesis of the gastritis.

Humanized anti-L-selectin antibody has beneficial effects on survival in a long-term in vivo model of hemorrhagic. traumatic shock.

This study was designed to test whether thrombomodulin is shed in septic baboons and whether shedding is blocked by antibody to tumor necrosis factor (anti-TNF). Live Escherichia coli were injected intravenously into 24 baboons according to one of the following regimens: 5 x 10(8) or 2 x 10(9) cfu/kg (n = 6/8), 2 x 10(9) cfu/kg with placebo (n = 5), or pretreatment with 1 mg/kg anti-TNF 2 h before E. coli injection (n = 5). E. coli administration resulted in a significant release of thrombomodulin in a dose-dependent manner; however, thrombomodulin release was significantly attenuated (180 to 40 ng/mL) by anti-TNF pretreatment. This is parallel to the reduction of neutrophil activation (elastase). These results provide evidence for an E. coli dose-related and TNF-dependent thrombomodulin release into the plasma of septic baboons and suggest a possible role of anti-TNF in protection of the endothelium.

The role of tumor necrosis factor (TNF) in interleukin (IL)-8 release in septicemia in the baboon (2-h infusion of live Escherichia coli, 5 x 10(8) cfu/kg) was investigated. Four experiments were done: one control (n = 7) and three with pretreatment to reduce TNF plasma levels. Pretreatment was with anti-TNF antibody (anti-TNF) 15 mg/kg, which neutralized circulating TNF (n = 4); 0.5 mg/kg of anti-TNF, which reduced peak TNF from 6.2 ng/mL (controls) to 0.6 ng/mL (n = 4); and a xanthine derivate (HWA138), which reduced TNF to 1 ng/mL (n = 5). With TNF levels < 1 ng/mL, a significant reduction of circulating IL-8 from 10.4 ng/mL (peak) in controls to 1 ng/mL (peak) in anti-TNF-treated animals was found, but with HWA138 only some decrease in IL-8 was seen. Despite high endotoxin levels (10-30 ng/mL peak), neutralization of TNF resulted in diminished release of IL-8 and significantly lower levels of granulocyte elastase.

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