Reactive oxygen species facilitate the in vitro and in vivo lipopolysaccharide-induced release of tumor necrosis factor.
Secretion of TNF from mouse peritoneal macrophages exposed to LPS in vitro was enhanced in the presence of H2O2 or sodium periodate. Neither of these agents induced release of TNF in the absence of LPS. Both iron chelators and free radical scavengers inhibited this enhanced secretion of TNF, implying the involvement of free radicals via a Fenton-type reaction. Oxidant stress, in the form of alloxan or divicine, also enhanced serum levels of TNF in mice made sensitive to LPS by low-level infection with malaria, and then given i.v. LPS. Pretreatment with the iron chelator, desferal, or the free radical scavenger, BHA, inhibited TNF release in these animals. Less TNF was also detected in mice given desferal before LPS in the absence of exogenous radical generator. These results could have implications for understanding the details of the MLR, the adherence of neutrophils to the walls of pulmonary vessels in free radical-induced lung pathology, and the side effects of bleomycin.
Chaudhri
G
G
John Curtin School of Medical Research, Australian National University, Canberra, ACT.
Clark
I A
IA
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D002083:Butylated Hydroxyanisole / Q000008:administration & dosage / Q000494:pharmacology; D002084:Butylated Hydroxytoluene / Q000008:administration & dosage / Q000494:pharmacology; D003676:Deferoxamine / Q000008:administration & dosage / Q000494:pharmacology; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology; D005609:Free Radicals; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D010100:Oxygen / Q000633:toxicity*; D010529:Peritoneal Cavity; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D000975:Antioxidants; D004095:Dihydropyridines; D005609:Free Radicals; D008070:Lipopolysaccharides; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D002084:Butylated Hydroxytoluene; D002083:Butylated Hydroxyanisole; D003676:Deferoxamine; D010100:Oxygen; C050223:desferrithiocin