In vivo neutralization of tumor necrosis factor attenuates the generalized Shwartzman reaction in the rabbit

Abstract

A role for tumor necrosis factor (TNF) and TNF-induced tissue factor (TF) expression has been postulated in endotoxin (LPS)-induced diffuse intravascular coagulation (DIC). We studied the protective efficacy of goat polyclonal gammaglobulin (lgG) against recombinant human (rh)-TNF in the generalized Shwartzman reaction (GSR) in rabbits, a model of DIC. Administration of anti-rhTNF 2 h before the first, preparative, LPS injection afforded 95% neutralization of TNF released during the GSR. Compared to saline-pretreated controls, a modest attenuation of fibrin deposition in kidney, lung, liver and spleen was observed 4 h after the second provocative LPS injection. Except for the lung, fibrin deposition in the anti-rhTNF group was not attenuated compared to the non-immune goat IgG (ni-lgG)-pretreated group. Both ni-lgG and anti-rhTNF prevented LPS-induced TF expression by mononuclear cells, but not by isolated glomeruli. Other mediators than TNF and TF are involved as well in glomerular injury and fibrin deposition after LPS.