Intravenous (i.v.) drug abuse is a primary risk factor in contraction of AIDS. Opiates and cocaine are frequently abused intravenously, and often are abused simultaneously. Marijuana and alcohol abuse is also common with i.v. drug abusers. Results from in vivo and in vitro studies have indicated that each of these drugs of abuse have immunomodulatory, and sometimes immunocompromising potential. Indeed, immunodepression often associates with i.v. heroin addiction even in the absence of HIV infection. Because of this information, drugs of abuse are suspected of altering host susceptibility to AIDS. This possibility constitutes the central theme of this research proposal. Clinical observations of the effect of drugs of abuse on immune parameters are difficult to interpret because of the complexities of the addiction milieu. For this reason, we have selected an in vitro approach to learn how such drugs influence host immunity. Cytofluorometric assays developed in our laboratory for detection of drug-induced modulation of lymphocyte-surface antigenic markers (receptors) will be used to define the independent and interdependent effects of selected drugs of abuse on regulation of various lymphocyte marker/receptor molecules that can be shown to be relevant to development of AIDS (i.e. CD2, CD4, CD8, CD3, and Class I and Class II HLA markers). The pharmacological specificity of opiate receptors involved in modulating expression of these lymphocyte markers will be defined by using various opiate agonists, antagonists, and their inactive enantiomers. The ability of selected drugs of abuse to modulate replication of lymphocytes stimulated by monoclonal antibody pairs specific to different classes of CD2 epitopes and by lectins will also be evaluated. The physiological basis for the pharmacological and immunological effects of the abused drugs to be studied will be determined through manipulation of transmembranal flow and intracellular mobilization of the major physiologically relevant anions (Na+, K+, Ca++). The data from these studies will be analyzed to determine which antigenic markers are modulated by drugs of abuse and how these drugs exert their effects. This information will then be used in judging how drugs of abuse influence the susceptibility of drug abusers to contraction of AIDS.
