Direct cellular immunomodulation produced by diacetylmorphine (heroin) or methadone

1. Abuse of the narcotic drug diacetylmorphine (heroin), as well as methadone, a drug for treating heroin addiction, has been associated with alterations in immune function in humans. The current study was performed to assess the direct (in vitro) immunomodulatory effect of exposure to these drugs, in view of the very limited studies reported thus far on this effect. 2. Murine splenocytes or peritoneal macrophages were cultured in vitro at concentrations of 0.0001-100 microM heroin or methadone. B-cell function was assessed by quantitating cellular proliferation in response to stimulation with an antigen analog; T-cell regulatory function was assessed by culturing splenocytes with or without drugs in the presence of anti-CD3 antibody and subsequently quantitating cytokine production; and T-cell effector function was evaluated by culturing lymphocytes with or without drugs during a 5-day induction culture 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 resulted in decreased B-cell proliferation at concentrations of 1-100 microM, and methadone had a similar effect at concentrations of 0.1-100 microM. 4. Production of IL-2 was suppressed by 0.1-100 microM of heroin, whereas exposure to methadone appeared to result in a generalized modulation, with suppression of IL-2 at most concentrations. In contrast, IL-4 production was only affected at the 100 microM concentration of both drugs.(ABSTRACT TRUNCATED AT 250 WORDS)