PROTECTIVE EFFECT OF LPS AND POLY A-U AGAINST IMMUNE OXIDATIVE INJURY- ROLE OF THIOLS RELEASED BY ACTIVATED MACROPHAGES

Oxidative injury of immune cells has been observed both at inflammator y sites and in pathologic situations, such as human immunodeficiency v irus infection. We used an ex vivo model of immune oxidative injury to test the antioxidant effect of two immunomodulating agents administer ed to C57B1/6 mice. Lipopolysaccharide (LPS) and the synthetic polyrib onucleotide poly A:U preserved the ConA-induced proliferative response of spleen T cells against oxidative injury ex vivo. The glutathione a nd thiol contents of fresh spleen T cells from LPS- and poly A:U-treat ed mice were significantly higher than control values. In addition, sp leen T cells from LPS- and poly A:U-treated mice were protected agains t the oxidative injury-induced decrease in glutathione content after 4 8 h of ConA stimulation. Because LPS and poly A:U both activate macrop hages, we sought an antioxidant effect of macrophage-released compound s. Neither rhIL-1 alpha nor rhTNF alpha protected against oxidative in jury in vitro. In contrast, LPS and poly A:U induced macrophages to re lease acid-soluble thiols, which have been reported to participate in the regulation of glutathione levels in lymphocytes and could therefor e protect against immune oxidative injury.