Improved survival of tumour necrosis factor-deficient mice during zymosan-induced multiple organ dysfunction syndrome

Autor: T. J. H. Volman, T. Hendriks, R. J. A. Goris, B. J. Kullberg
Rok vydání: 2000
Předmět:
Zdroj: British Journal of Surgery. 87:931-931
ISSN: 1365-2168
0007-1323
Popis: Background Tumour necrosis factor (TNF) is believed to be a crucial mediator in systemic inflammation and the multiple organ dysfunction syndrome (MODS). Previous studies in this laboratory with a murine model have shown that interventions directed at TNF could mitigate the symptoms of zymosan-induced MODS. The present study aimed to investigate the course of MODS in the absence of TNF. Methods Twenty-four TNF/LT-knockout (−/−) mice and 25 wild-type (+/+) mice received an intraperitoneal dose of lipopolysaccharide 40 μg, followed by zymosan 1 mg per g body-weight 6 days later (day 0). Survival, body-weight and body temperature were monitored. At day 22 ten −/− mice and five +/+ mice were killed, and organs were collected and weighed. The remaining animals were followed until day 48, when all were killed and their organs harvested for histological examination. Results In all animals zymosan induced an acute sterile peritonitis phase followed by an apparent recovery. From day 8 onwards the +/+ mice entered a third, MODS-like, phase, characterized by loss of body-weight, decreased body temperature and significant mortality rate. At day 22, survival in the −/− mice was 92 per cent, which was significantly (P < 0·05) higher than that in the +/+ mice (60 per cent). In addition, mean body temperature and mean relative body-weight (versus weight at day 0) were 33·3°C and 84 per cent respectively in the +/+ mice. Data for the −/− mice were 35·9°C and 100 per cent respectively (P < 0·05). However, at this time point, both the +/+ mice and the −/− mice showed significant and similar organ damage, indicated by an increase in absolute and relative (versus body-weight) weight of lung, spleen and liver (the last organ only in the −/− mice). Moreover, at day 48 histopathological examination of liver, lungs, spleen and kidneys from the surviving animals showed a similar degree of microscopic damage in both the −/− and +/+ mice. Conclusion TNF-deficient mice exhibit significantly improved survival during zymosan-induced MODS and their clinical condition appears to be better than that of wild-type animals. However, surviving animals from both groups eventually display a similar degree of organ damage. Thus, in this murine model, the absence of TNF does not completely protect against MODS.
Databáze: OpenAIRE
Externí odkaz: