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

Yoshihiko Ueda, Hon Kwang Lee, Shogo Ito, Kenichi Saito, Neal Niesen, Jan R. Brentjens, Reinold O.B. Gans

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)67-75
Number of pages9
JournalInnate Immunity
Volume3
Issue number1
DOIs
Publication statusPublished - 1996
Externally publishedYes

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