THE EFFECT OF ENDOTOXIN AND ENDOTOXIN TOLERANCE ON INFLAMMATION INDUCED BY MYCOBACTERIAL ADJUVANT

  • 1 January 1983
    • journal article
    • research article
    • Vol. 56  (4) , 293-301
Abstract
Since repeated administration of lipopolysaccharide [LPS] produces tolerance i.e., resistance to the toxic and inflammatory effects of LPS, the effect of LPS and/or LPS tolerance on inflammation due to mycobacterial adjuvant was tested. Male Sprague-Dawley rats were injected with Escherichia coli LPS or saline i.p. and then challenged with 100 .mu.g killed Mycobacterium butyricum (adjuvant) in the footpad. A single dose of 100 .mu.g LPS 3 or 24 h before adjuvant markedly, but transiently reduced the local footpad swelling that begins within hours of the adjuvant injection and histologically resembles a sterile abscess. Animals that received multiple doses of LPS and were therefore tolerant or animals that received LPS 72 h before adjuvant demonstrated adjuvant-induced footpad swelling nearly equal to controls. The anti-inflammatory effect of LPS was transient since footpad swelling in all groups was nearly comparable 6 days after the adjuvant injection and LPS failed to inhibit consistently the arthritis that develops .gtoreq. 22 wk after adjuvant injection. Thus, LPS can markedly inhibit the prodrome of adjuvant arthritis (footpad swelling due to M. butyricum); inhibition of this prodrome does not prevent subsequent development of arthritis; LPS tolerance diminishes this anti-inflammatory effect of LPS.