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 inflammatory sites and in pathologic situations, such as human immunodeficiency virus infection. We used an ex vivo model of immune oxidative injury to test the antioxidant effect of two immunomodulating agents administered to C57B1/6 mice. Lipopolysaccharide (LPS) and the synthetic polyribonucleotide poly A:U preserved the ConA-induced proliferative response of spleen T cells against oxidative injury ex vivo. The glutathione and thiol contents of fresh spleen T cells from LPS- and poly A:U-treated mice were significantly higher than control values. In addition, spleen T cells from LPS- and poly A:U-treated mice were protected against the oxidative injury-induced decrease in glutathione content after 48 h of ConA stimulation. Because LPS and poly A:U both activate macrophages, we sought an antioxidant effect of macrophage-released compounds. Neither rhIL-lα nor rhTNFα protected against oxidative injury in vitro. In contrast, LPS and poly A:U induced macrophages to release acid-soluble thiols, which have been reported to participate in the regulation of glutathione levels in lymphocytes and could therefore protect against immune oxidative injury.