PREVENTION OF ENDOTOXIN-INDUCED ACUTE LETHALITY IN PROPIONIBACTERIUM ACNES-PRIMED RABBITS BY AN ANTIBODY TO LEUKOCYTE INTEGRIN BETA(2) WITHCONCOMITANT REDUCTION OF CYTOKINE PRODUCTION
N. Ikeda et al., PREVENTION OF ENDOTOXIN-INDUCED ACUTE LETHALITY IN PROPIONIBACTERIUM ACNES-PRIMED RABBITS BY AN ANTIBODY TO LEUKOCYTE INTEGRIN BETA(2) WITHCONCOMITANT REDUCTION OF CYTOKINE PRODUCTION, Infection and immunity, 63(12), 1995, pp. 4812-4817
Acute lethality was induced in rabbits by the sequential injection of
Propionibacterium acnes and lipopolysaccharide (LPS). P. acnes induced
the infiltration of inflammatory cells into the liver lobules during
the early phase, and LPS in the late phase caused death in association
with pathological changes mimicking hepatocellular necrosis or degene
ration around infiltrated mononuclear cells and fibrin deposition in t
he liver, lung, and kidney, suggestive of a systemic Schwartzman-like
reaction. These pathological changes were accompanied by the elevation
of plasma tumor necrosis factor (TNF) and interleukin-8 (IL-8) levels
. A neutralizing antibody to a leukocyte adhesion molecule, integrin b
eta(2) (CD18), administered at the time of LPS challenge, prevented he
patocellular injury and fibrin deposition and improved the survival ra
tes. Unexpectedly, the antibody reduced the elevation of plasma TNF an
d IL-8 levels, An anti-TNF alpha antibody but not an anti-IL-8 antibod
y prevented the acute lethality induced by P. acnes and LPS, confirmin
g that TNF alpha is an essential mediator in this model. These results
indicate that CD18 is critically involved in vivo in activating leuko
cytes to produce cytokines in response to LPS.