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- Title
Effect of postponed treatment with an anti-tumour necrosis factor (TNF) F(ab')<em>2</em> fragment on endotoxin--induced cytokine and neutrophil responses in chimpanzees.
- Authors
van der Poll, T.; Levi, M.; Cate, H. Ten; Jansen, J.; Biemond, B. J.; Haagmans, B. L.; Eerenberg, A.; van Deventer, S. J. H.; Hack, C. E.; Cate, J. W. Ten
- Abstract
TNF is considered to be an intermediate factor in endotoxin-induced release of other cytokines and endotoxin-induced neutrophil degranulation. Little is known about the effect of postponed treatment with anti-TNF in primate endotoxin models. To assess the effect of delayed treatment with anti-TNF in endotoxaemia, six healthy adult chimpanzees were intravenously injected with Escherichia coli endotoxin (4 ng/kg). In three of these animals the administration of endotoxin was followed after 30 mm by a bolus i.v. injection of the anti-TNF F(ab')2 fragment MAK 195F(0-1 mg/kg). Post-treatment with MAK 195F completely prevented the appearance of TNF activity in serum elicited by endotoxin, and markedly reduced the rises in the serum concentrations of IL-6 and IL-8. In addition, the endotoxin-induced increases in the type I and type 11 soluble TNF receptors were also profoundly inhibited by MAK 195F. suggesting that TNF is involved in the release of its own soluble ceceptors in endotoxacmia. Neutrophilic leucocytosis was not affected by MAK 19SF. In contrast, MAK 195F did significantly abrogate neutrophil degranulation. as measured by the plasma concentrations of lactoferrin. These results indicate that treatment with anti-TNF 30 mm after the administration of endotoxin is still effective in attenuating the induction of the cytokine network and of neutrophil degranulation.
- Subjects
ENDOTOXINS; CELLULAR immunity; CYTOKINES; BLOOD plasma; GROWTH factors; ENTEROBACTERIACEAE
- Publication
Clinical & Experimental Immunology, 1995, Vol 100, Issue 1, p21
- ISSN
0009-9104
- Publication type
Article