COCAINE INHIBITS PRODUCTION OF MURINE HEPATITIS-VIRUS BY PERITONEAL-MACROPHAGES IN-VITRO

Our previous studies have demonstrated a number of effects of cocaine on macrophage (Mo) functions. The present studies were initiated to as certain the effects of cocaine on virus production in vitro. C57BL/6 m ice were injected intraperitoneally with thioglycollate broth, and the peritoneal Mo collected 4 days later were cultured in 96-well microti ter plates as continuous monolayers. Various concentrations of cocaine were incubated with Mo for up to 5 days. Mouse hepatitis virus (MHV) was added to these cultures, which was followed by a methyl cellulose overlay. Cocaine caused a dose-dependent inhibition of viral plaques a fter 48 hr of incubation. The inhibitory activity was transferable to fresh cultures of Mo, inhibiting both plaque size and number. Specific polyclonal antibodies to alpha + beta-interferon but not tumor necros is factor or transforming growth factor-beta partially reversed the in hibition of both plaque size and plaque number. It appears that MHV in duced interferon in cultured Ms, an effect that was enhanced by cocain e. Since cocaine has been reported to interfere with calcium mobilizat ion, studies were done using ionomycin, a calcium ionophore, in order to reverse possible effects on intracellular calcium that could affect virus production. The presence of ionomycin completely reversed the i nhibition of virus production by cocaine. The antiviral effects of coc aine appear to be caused by modulation of intracellular calcium and, t o a lesser extent, by the enhancement of interferon production.