Interferon‐α prevents endotoxin‐induced mortality in mice

Shie‐Pon ‐P Tzung, Thomas C. Mahl, Peter Lance, Valerie Andersen, Stefan A. Cohen

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Endotoxins, the lipopolysaccharide (LPS) moieties on the bacterial cell wall, cause many of the pathological features of Gram‐negative septicemia. Tumor necrosis factor (TNF), primarily a product of monocyte/macrophages, has been shown to mediate many of the pathophysiological effects of endotoxin. Kupffer cells, the largest macrophage population in the body, release TNF when stimulated by LPS in vitro. A recombinant human hybrid interferon‐α A/D (rIFN‐α) markedly inhibited this LPS‐elicited TNF production by Kupffer cells. The effects of rIFN‐α were further tested in C57BL/6 mice receiving a lethal dose (400 μg/mouse) of LPS. All LPS‐treated mice died within 2 days. Pretreatment with rIFN‐α 1 h before LPS challenge improved the survival at 3 days to 22% (5/23, p < 0.04). In contrast, rIFN‐α was more effective when administered 20 min after LPS injection, increasing the survival rate to 81% (13/16, p < 0.0001). TNF mRNA expression in the liver and spleen 50 min after LPS challenge, and plasma TNF 1.5 h after LPS were also reduced by either pretreatment or post‐treatment with rIFN‐α. Subsequently, experiments were carried out to test the efficacy of delayed rIFN‐α treatment. A significant protective effect was still apparent when rIFN‐α was administered 6, 10 and even 14 h (81%, 62% and 28% survival, respectively) after LPS challenge when serum TNF levels had already returned to near baseline. These experimental results suggest that rIFN‐α might have a therapeutic potential for the prevention and treatment of the deleterious effects associated with endotoxemia besides mechanisms initially blocking TNF production.

Original languageEnglish (US)
Pages (from-to)3097-3101
Number of pages5
JournalEuropean Journal of Immunology
Volume22
Issue number12
DOIs
StatePublished - Dec 1992
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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