INHALATION EXPOSURE TO ISOBUTYL NITRITE INHIBITS MACROPHAGE TUMORICIDAL ACTIVITY AND MODULATES INDUCIBLE NITRIC-OXIDE

Abuse of nitrite inhalants is common among male homosexuals and a hist ory of abuse has been correlated with seropositivity to HIV and with t he incidence of Kaposi's sarcoma among AIDS patients. The present stud y shows that inhalation exposure of mice to 900 ppm isobutyl nitrite f or 45 min/day for 14 days compromised macrophage tumoricidal activity by up to 40% and it remained compromised for at least 7 days after ter minating exposures. The inhalation exposures did not affect tumor cell binding but did inhibit inducible nitric oxide (NO.). The NO. synthas e inhibitor N-G-methyl-L-arginine totally inhibited both NO. productio n and cytotoxicity, suggesting that reductions in NO. due to inhalant exposure may be responsible for the reduced cytotoxic activity. Exposu re to the inhalant increased constitutive production of tumor necrosis factor-alpha (TNF-alpha). TNF-alpha has been reported to stimulate th e replication of HIV and the proliferation of Kaposi's sarcoma cells i n vitro.