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Diminished Interleukin-6 Response to Proinflammatory Challenge in Men and Women after Intravenous Cocaine Administration

Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School (J.H.H., M.B.S., N.K.M., J.H.M., A.J.S.), Belmont, Massachusetts 02478; and Departments of Psychiatry (J.H.H.) and Orthopedic Surgery (J.G.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115

Address all correspondence and requests for reprints to: John H. Halpern, M.D., Alcohol and Drug Abuse Research Center, McLean Hospital, 115 Mill Street, Belmont, Massachusetts 02478-9106. E-mail: john_halpern{at}hms.harvard.edu.

Cocaine abuse is associated with increased rates of infections, including human immunodeficiency virus, and cocaine has immunomodulatory effects in experimental animal and cellular models. When challenged by antigens, tissues release cytokine polypeptides that signal a complex balance of cellular and humoral immune responses. Placement of indwelling venous catheters also leads to surrounding tissue inflammation, mediated partially by local production and release of the proinflammatory cytokine, IL-6. Thus, catheter placement provides a model for examination of cocaine’s immunological effects. Thirty healthy men and women with a history of cocaine use participated in this study of neuroendocrine and immunological responses to iv injection of 0.4 mg/kg cocaine or saline placebo. After injection, blood samples were collected from the antecubital vein of the opposite arm via an indwelling venous catheter at 2, 4, 8, 12, 16, 20, 30, 40, 60, 80, 120, 180, and 240 min. Cocaine, ACTH, cortisol, and dehydroepiandrosterone concentrations peaked at 8, 12, 40, and 20 min, respectively. Stimulation of IL-6 at 240 min was markedly reduced in subjects receiving cocaine compared with subjects receiving placebo (3.85 ± 0.49 vs. 11.64 ± 2.21 pg/ml; P = 0.0019, by two-tailed t test). Gender and menstrual cycle phase did not significantly influence most endocrine or IL-6 measures, although the small number of subjects limits the power of these comparisons. Because cocaine stimulates the hypothalamic-pituitary-adrenal axis, IL-6 suppression may be a consequence of corticosteroid release. Cocaine-induced suppression of proinflammatory IL-6 may mediate impaired host defenses to infections.

This work was supported by Grants P01-DA-14528, P50-DA-04059, K23-DA-00494, T32-DA-07252, KO5-DA-00064, and KO5-DA-00101 from the National Institute on Drug Abuse, National Institutes of Health.

Abbreviations: AUC, Area under the curve; CRF, corticotropin-releasing factor; DHEA, dehydroepiandrosterone; hCG, human chorionic gonadotropin; HIV, human immunodeficiency virus; HPA, hypothalamic-pituitary-adrenal; IFN-, interferon-.

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