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Endotoxin tolerance diminishes certain antiinflammatory effects of endotoxin

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Abstract

Endotoxin (bacterial lipopolysaccharide, LPS) is paradoxically both inflammatory and antiinflammatory. A single intravenous injection of 100μgEscherichia coli LPS markedly inhibits the inflammatory changes associated with cutaneous reversed passive Arthus (RPA) reactions in New Zealand white rabbits. Polymorphonuclear (PMN) leukocytes from LPS-treated rabbits exhibit diminished responsiveness in vitro to complement (C5) -derived peptides. Repeated injections of LPS render animals “tolerant”, that is, refractory to the toxic and inflammatory efects of LPS. We examined whether tolerance would enhance the ability of LPS to inhibit inflammation not attributable to LPS. Surprisingly, as compared with rabbits receiving a single dose of LPS, tolerant rabbits demonstrated greater inflammatory changes (i.e., PMN exudation, vascular permeability) associated with RPA reactions. PMNs from LPS-tolerant rabbits responded in vitro to C5-derived peptides significantly more than PMNs from rabbits that received a single dose of LPS. We speculate that some antiinflammatory effects of LPS require the toxic or inflammatory effects of LPS itself. These observations might relate to the limited efficacy of fever therapy and the variable effects of gram-negative sepsis on functions of human PMNs.

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Author notes

  1. James T. Rosenbaum

    Present address: Kuzell Institute for Arthritis Research, Medical Research Institute of San Francisco at Pacific Presbyterian Medical Center, 2200 Webster Street, R 305, 94115, San Francisco, California

Authors and Affiliations

  1. Department of Medicine, The Rosalind Russell Arthritis Research Laboratory, USA

    James T. Rosenbaum, Kaija T. Hartiala & Ira M. Goldstein

  2. Department of Pathology, University of California, San Francisco

    Edward L. Howes Jr.

  3. San Francisco General Hospital, 94110, San Francisco, California

    Edward L. Howes Jr.

Authors
  1. James T. Rosenbaum
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  2. Kaija T. Hartiala
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  3. Edward L. Howes Jr.
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  4. Ira M. Goldstein
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Rosenbaum, J.T., Hartiala, K.T., Howes, E.L. et al. Endotoxin tolerance diminishes certain antiinflammatory effects of endotoxin. Inflammation 9, 297–308 (1985). https://doi.org/10.1007/BF00916278

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