ROLE OF TUMOR-NECROSIS-FACTOR-ALPHA AND GLUCOCORTICOID ON LIPOPOLYSACCHARIDE (LPS)-INDUCED APOPTOSIS OF THYMOCYTES

Administration of bacterial lipopolysaccharide (LPS) into mice markedl y induced the apoptosis of CD4(+)8(+) thymocytes. The injection of ant i-tumor necrosis factor (TNF)-alpha antibody or RU38486, a glucocortic oid receptor antagonist, into mice definitely inhibited LPS-induced ap optosis of thymocytes. Addition of the sera 1 h after injection of LPS into in vitro cultures of thymocytes caused thymocyte apoptosis. It w as also prevented by either anti-TNF-Lu antibody or RU38486. Further. recombinant TNF-alpha and hydrocortisone collaborated in induction of the thymocyte apoptosis in vitro. The in vivo phenomenon of LPS-induce d apoptosis of thymocytes was reproducible by the in vitro experimenta l system. It was therefore suggested that both TNF-alpha and glucocort icoid participate and collaborate as effector molecules in LPS-induced apoptosis of thymocytes.