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Pablo León, MD; H. Paul Redmond, FRCSI; Jian Shou, MD; John M. Daly, MD

Arch Surg. 1992;127(2):146-151.

Abstract
• Endotoxin (lipopolysaccharide [LPS])—induced cytokine release has been implicated in the pathogenesis of sepsis. Sublethal doses of LPS induce tolerance to a septic insult. This study evaluated pretreatment with interleukin 1 (IL-1) against an LPS challenge and examined its relationship to endotoxin tolerance. C3H/HeN mice (N=100) were injected intraperitoneally with phosphate-buffered saline (control group), IL-1 (200 µg/kg), or LPS (1 mg/kg) for 3 days. On day 5, peritoneal macrophages were harvested and assayed for antimicrobial activity (superoxide anion production and Candida albicans phagocytosis). Serum cytokine levels and survival after an LPS challenge on day 5 were also assessed. Pretreatment with IL-1 or LPS significantly increased superoxide anion production, C albicans phagocytosis, and survival compared with pretreatment with phosphate-buffered solution. Interleukin 6 levels significantly decreased in the IL-1 and LPS groups. Peak levels of tumor necrosis factor significantly decreased only in the LPS group. Thus, pretreatment with IL-1 or low doses of LPS may exert protective effects by decreasing levels of interleukin 6 while increasing antimicrobial activity. Mice pretreated with IL-1 were protected from endotoxin despite elevated peak levels of tumor necrosis factor, suggesting a different mechanism for endotoxin tolerance than for tolerance to tumor necrosis factor.

(Arch Surg. 1992;127:146-151)

Author Affiliations
From the Department of Surgery and the Harrison Department of Surgical Research, University of Pennsylvania, Philadelphia.

Footnotes
Accepted for publication November 29, 1991.

Presented at the 11th Annual Meeting of the Surgical Infection Society, Fort Lauderdale, Fla, April 15, 1991.

Reprints not available.

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