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

Yoshihiko Ueda

Department of Pathology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA

Kwang Hoon Lee

Department of Pathology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA

Shogo Ito

Department of Pathology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA

Kenichi Saito

Department of Pathology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA

Neal Niesen

Department of Pathology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA

Jan R. Brentjens

Department of Pathology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA

Reinold O.B. Gans

Department of Pathology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA

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.

Journal of Endotoxin Research, Vol. 3, No. 1, 67-75 (1996)
DOI: 10.1177/096805199600300108
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