PREVENTION OF ENDOTOXIN-SHOCK BY AN ANTIBODY AGAINST LEUKOCYTE INTEGRIN BETA(2) THROUGH INHIBITING PRODUCTION AND ACTION OF TNF

Septic shock remains a serious disorder associated with high mortality . Accumulating evidence indicates that TNF is a major and essential me diator of endotoxin shock. We report here that administration of an an tibody against CD18 dramatically reduced endotoxin-induced shock in ra bbits as revealed by prevention of severe hypotension, metabolic acido sis and a pathological change suggestive of disseminated intravascular coagulation with concomitant inhibition of elevation of plasma TNF ac tivity, The anti-CD18 antibody also inhibited the hypotension induced by administering recombinant TNF. Furthermore, an antibody against a l igand for CD18 complexes, intercellular adhesion molecule-1, also prev ented TNF-induced shock as well as endotoxin shock in rabbits. These o bservations suggest that adhesion of leukocytes to endothelium may be of primary importance in the action of INF as well as in the productio n of TNF in vivo and that the antibody against adhesion molecules coul d be of therapeutic benefit in life-threatening septic shock in humans .