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 (M phi) functions. The present studies were initiated to ascertain the effects of cocaine on virus production in vitro. C57BL/6 mice were injected intraperitoneally with thioglycollate broth, and the peritoneal M phi collected 4 days later were cultured in 96-well microtiter plates as continuous monolayers. Various concentrations of cocaine were incubated with M phi 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 after 48 hr of incubation. The inhibitory activity was transferable to fresh cultures of M phi, inhibiting both plaque size and number. Specific polyclonal antibodies to alpha + beta-interferon but not tumor necrosis factor or transforming growth factor-beta partially reversed the inhibition of both plaque size and plaque number. It appears that MHV induced interferon in cultured M phi, an effect that was enhanced by cocaine. Since cocaine has been reported to interfere with calcium mobilization, 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 inhibition of virus production by cocaine. The antiviral effects of cocaine appear to be caused by modulation of intracellular calcium and, to a lesser extent, by the enhancement of interferon production.
Lefkowitz
S S
SS
Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
Brown
D J
DJ
Grattendick
K
K
Lefkowitz
D L
DL
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003042:Cocaine / Q000494:pharmacology*; D017077:Culture Media, Conditioned; D005260:Female; D007106:Immune Sera / Q000276:immunology; D016899:Interferon-beta / Q000096:biosynthesis; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000821:virology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D006517:Murine hepatitis virus / Q000502:physiology*; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects
D017077:Culture Media, Conditioned; D007106:Immune Sera; D007476:Ionophores; D008070:Lipopolysaccharides; D015759:Ionomycin; D016899:Interferon-beta; D003042:Cocaine; D002118:Calcium