DIRECT CELLULAR IMMUNOMODULATION PRODUCED BY DIACETYLMORPHINE (HEROIN) OR METHADONE

1. Abuse of the narcotic drug diacetylmorphine (heroin), as well as me thadone, a drug for treating heroin addiction, has been associated wit h alterations in immune function in humans. The current study was perf ormed to assess the direct (in vitro) immunomodulatory effect of expos ure to these drugs, in View of the very limited studies reported thus far on this effect. 2. Murine splenocytes or peritoneal macrophages we re cultured in vitro at concentrations of 0.0001-100 mu M heroin or me thadone. B-cell function was assessed by quantitating cellular prolife ration in response to stimulation with an antigen analog; T-cell regul atory function was assessed by culturing splenocytes with or without d rugs in the presence of anti-CD3 antibody and subsequently quantitatin g cytokine production; and T-cell effector function was evaluated by c ulturing lymphocytes with or without drugs during a 5-day induction cu lture followed by assessment of specific cytotoxic T-lymphocyte (CTL) activity. Natural immunity was assessed by quantitating basal and IL-2 augmented natural killer (NK) cell function, and macrophage function was assessed by cytokine production. 3. In vitro exposure to heroin re sulted in decreased B-cell proliferation at concentrations of 1-100 mu M, and methadone had a similar effect at concentrations of 0.1-100 mu M. 4. Production of IL-2 was suppressed by 0.1-100 mu M of heroin, wh ereas exposure to methadone appeared to result in a generalized modula tion, with suppression of IL-2 at most concentrations. fn contrast, IL -4 production was only affected at the 100 mu M concentration of both drugs. CTL was suppressed by exposure to 100 mu M heroin, whereas NK c ell activity was suppressed at high concentrations of both heroin and methadone, and macrophage function was also differentially affected. 5 . The results presented here indicate that both drugs display some imm unomodulatory potential.