A monoclonal antibody against tumour necrosis factor-alpha improves survival in experimental multiple organ dysfunction syndrome.
A single intraperitoneal administration of zymosan induces multiple organ dysfunction syndrome (MODS) in C57BL/6 mice. The authors investigated the effect of a monoclonal antibody V1q against murine tumour necrosis factor alpha (TNF-alpha) on the development of zymosan-induced MODS and on plasma concentrations and the production capacity of interleukin 6 (IL-6) by peritoneal cells. C57BL/6 mice received doses of V1q starting either simultaneously with administration of zymosan every four days, or from 4 or 8 days after administration of zymosan onwards. The animals were monitored for survival, condition, and body weight and temperature. Twelve days after zymosan all surviving animals were killed to obtain plasma, organs and peritoneal cells. Plasma concentrations of IL-6 and lipopolysaccharide-stimulated production of IL-6 by peritoneal cells were measured; organs were weighed as an indicator for organ damage and lung damage was assessed macroscopically. Survival improved when the animals were treated with V1q starting at either time point, and a subpopulation developed from the group receiving V1q from day 0 onwards that displayed improved body weight and temperature when compared to the animals receiving zymosan only. Also, the wet organ weights improved in this subgroup, indicating a beneficial effect of the monoclonal antibody. However, V1q administered could neither decrease the circulating IL-6 concentrations toward control values, nor did V1q treatment normalize IL-6 production capacity (stimulated or unstimulated). The development of zymosan-induced MODS can be attenuated by the monoclonal antibody V1q.
Jansen
M J
MJ
Department of Surgery, University Hospital Nijmegen, Nijmegen, P.O. Box 6101, 6500 HB, The Netherlands.
Hendriks
T
T
Hermsen
R
R
Van der Meer
J W
JW
Goris
R J
RJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009102:Multiple Organ Failure / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D015054:Zymosan
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan