Substance abuse and the immune system.

Study of the immunological effects of opioids has a long history starting at least a century ago. In 1898, working in the laboratory of the ‘father’ of cell mediated immunology, Elie Metchnikoff, Cantacuzene (1898) showed that morphine alters migratory and phagocytic capacities of macrophages. By the 1940s speculation had appeared that opiate addiction may be a proximal cause for increased severity of tuberculosis among opiate abusers (Hussey and Katz, 1950). Concern over the epidemiologic connection between heroin addiction and infectious disease was rekindled in the 1960s as blood supplies contaminated with hepatitis virus were found to be associated with intravenous drug abusers (IDA) (Sapira, 1968). Through the 1970s, reports continued to appear regarding immunological deficits in IDAs. Then, in 1979, Wybran and colleagues reported that functionally active opiate receptors appeared to be present on T cell lymphocytes themselves (Wybran et al., 1979). This seminal report was the most cited research paper of the early 1980s as it secured the neuroimmune connection of the endogenous opioid system. Many studies have followed (reviewed in Sharp, 1998), so that, today, endogenous opioids are no longer considered simply as neuropeptides but are regarded as part of the neuroimmune cytokine armimentarium. The question remains, though, as to the role of opiates in host defense against infection. This issue has assumed renewed prominence because of the high incidence of HIV-1 infections and AIDS among IDAs (Wormser et al., 1983). For well over a decade, the College on Problems of Drug Dependence (CPDD) has sponsored symposia and seminars on immune effects of opioids and other substances of abuse at their national meetings. The College continues to recognize and highlight the importance of research in this area because there are many fundamental biological issues to be unraveled that relate to the impact of substance abuse on immune function. And, of course, the threat to society of IDAs spreading infections like HIV-1 and hepatitis virus remains a major public health concern. The present issue of Drug and Alcohol Dependence, therefore, has been dedicated to updating knowledge of the immunological effects of opioids while illustrating the breadth of investigations necessary to bring the immunological roles of opioids into perspective. Though our topic here is opioids, this focus by no means is meant to limit an overall perspective on the importance of understanding how drugs of abuse, in general, impact on immune function. There is ample evidence that marijuana, cocaine, alcohol, and, most recently, methamphetamines all impact on immune processes so that the perspectives derived from the following reports should be regarded for their relevance to all forms of substance abuse. The current ‘special issue’ is opened by a review of the field by Dr McCarthy and colleagues from Dr Thomas Rogers’ laboratory at Temple University. Their report focuses on the direct effects of opiates on immune cells while recognizing also the importance of indirect effects. Pharmacological and molecular biological data are discussed that define the current state of knowledge about the presence of opioid receptors on cells of the immune system. Focus is also drawn to the connection between opioids and modulation of immune cytokines and how all of these considerations relate to opioid’s influence over infectious disease, especially HIV-1 infections and AIDS. The molecular theme is extended further in an article by Dr John Madden and colleagues at Emory University. Using molecular and pharmacological approaches, they were unable to identify classical neuronal mu opioid receptors on resting or activated human periph* Corresponding author. Present address: Emory West Campus, Room 506W, 1256 Briarcliff Road, Atlanta, GA 30306, USA. Tel.: +1-404-7129804; fax: +1-404-7129841. E-mail address: rdonaho@emory.edu (R.M. Donahoe).