Inhalation exposure to isobutyl nitrite inhibits macrophage tumoricidal activity and modulates inducible nitric oxide

Abstract

Abuse of nitrite inhalants is common among male homosexuals and a history of abuse has been correlated with seropositivity to HIV and with the incidence of Kaposi's sarcoma among AIDS patients. The present study shows that inhalation exposure of mice to 900 ppm isobutyl nitrite for 45 min/day for 14 days compromised macrophage tumoricidal activity by up to 40% and it remained compromised for at least 7 days after terminating exposures. The inhalation exposures did not affect tumor cell binding but did inhibit inducible nitric oxide (NO zero). The NO zero synthase inhibitor NG-methyl-L-arginine totally inhibited both NO zero production and cytotoxicity, suggesting that reductions in NO zero due to inhalant exposure may be responsible for the reduced cytotoxic activity. Exposure to the inhalant increased constitutive production of tumor necrosis factor-alpha (TNF-alpha). TNF-alpha has been reported to stimulate the replication of HIV and the proliferation of Kaposi's sarcoma cells in vitro.