Tumour necrosis factor alpha (TNF-alpha) and interleukin 6 in a zymosan-induced shock model.
TNF plays a central role in septic shock induced by endotoxin or Gram-negative bacteria. Zymosan can elicit a septic shock-like syndrome in rodents in the absence of endotoxin. TNF and IL-6 release in mice treated with zymosan was investigated. One hour after intraperitoneal zymosan injection, maximal TNF levels were measured in serum, followed by IL-6 peak levels 1 h later. Treatment with a monoclonal antibody against TNF lowered zymosan-induced mortality from 63 to 11.6%, while maximal IL-6 levels were lowered by about 40%. Mechanisms triggering zymosan-induced cytokine release in murine macrophages were analysed in vitro. Cytokine release was only slightly triggered by uncoated zymosan particles. Thirty-nine per cent of TNF release by macrophages appeared to be triggered by zymosan-bound activated complement. Maximal TNF release also required the presence of natural antibodies against zymosan and zymosan-activated serum. In contrast, maximal IL-6 release was reached upon stimulation with zymosan-activated serum only, while the presence of zymosan particles lowered this response. We conclude that TNF is a crucial mediator in zymosan-induced shock. TNF release can be induced by different immunological pathways, without the need for the direct presence of endotoxins. Although IL-6 release during septic shock is partly dependent on TNF, in vitro trigger mechanisms for IL-6 and TNF differ remarkably.
von Asmuth
E J
EJ
Department of Surgery, University of Limburg, Maastricht, The Netherlands.
Maessen
J G
JG
van der Linden
C J
CJ
Buurman
W A
WA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D003167:Complement Activation / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000097:blood*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D010529:Peritoneal Cavity / Q000166:cytology; D011897:Random Allocation; D012772:Shock, Septic / Q000276:immunology* / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*; D015054:Zymosan
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan