I Abbreviations used: ACTH, adrenocorticotropic hormone; ADCC, antibody-dependent cellular cytotoxicity; Bma .. total number of binding sites; BREM, bremazocine, an agonist with modest selectivity for K sites; CCK, cholecystokinin; ConA, concanavalin A; DADLE, [D-Ala2,D-LeuS]enkephalin, an agonist somewhat selective for /j �ites; DEX, dextrorphan, inert enantiomer of LEV; DHM, dihydromorphine, a Jl-selective agonist; DIP, dipre­ norphine, a relatively nonselective antagonist; DYN, dynorphin, a peptide product of the dynorphin gene, selective for K sites; EKC, ethylketazocine, a benzomorphan agonist with modest selectivity for K sites; END, endorphin; a peptide product of the pro-opio­ melanocortin gene; <Xand y-endorphin are fragments of fJ-endorphin; fJ-endorphin is selective for e sites; ETO, etorphine, a relatively nonselective agonist; fMLP, formyl-methio­ nyl-leucinyl-phenylalanine; granulo, granulocyte(s); h, human; ICso, concentration of a com­ peting ligand that reduces specific binding of radioligand by 50%; icv, intracerebro­ ventricular; IFN, interferon; ir-, immunoreactive; Kd, K;, equilibrium dissociation con­ stants, determined by binding isotherm or by competition, respectively; LENK, [Leu]en­ kephalin, a minor product of the pro-enkephalin gene, an agonist somewhat selective for {) sites; leuko, leukocyte(s); LEV, levorphanol, a Jl-selective agonist; Iympho, Iymphocyte(s); m, mouse; M.p, macrophage(s); MENK, [Met]enkephalin, major product of the pro-enkephalin gene, a /j-selective agonist; MNC, mononuclear cell(s); mono, monocyte(s); MOR, morphine, a Jl-selective agonist; NA, not applicable; NAL, naloxone, a moderately jl-selective antag­ onist; NK, natural killer; NR, not reported; NTX, naltrexone, a long-lasting Jl-selective antagonist closely related to naloxone; PBL, peripheral blood Iymphocyte(s); PBMNC, peripheral blood mononuclear cell(s); PHA, phytohemagglutinin; PMNL, polymorpho­ nuclear leukocyte(s); r, rat; RIA, radioimmunoassay; spleno, splenocyte; SRBC, sheep red blood cells; VIP, vasoactive intestinal peptide.

Opioid Peptides and Opioid Receptors in Cells of the Immune System

Localization of xanthine oxidase in mammary-gland epithelium and capillary endothelium.

Opioids, opioid receptors, and the immune response.

The use of recreational drugs of abuse has generated serious health concerns. There is a long-recognized relationship between addictive drugs and increased levels of infections. Studies of the mechanisms of actions of these drugs became more urgent with the advent of AIDS and its correlation with abused substances. The nature and mechanisms of immunomodulation by marijuana, opiates, cocaine, nicotine, and alcohol are described in this review. Recent studies of the effects of opiates or marijuana on the immune system have demonstrated that they are receptor mediated, occurring both directly via specific receptors on immune cells and indirectly through similar receptors on cells of the nervous system. Findings are also discussed that demonstrate that cocaine and nicotine have similar immunomodulatory effects, which are also apparently receptor mediated. Finally, the nature and mechanisms of immunomodulation by alcohol are described. Although no specific alcohol receptors have been identified, it is widely recognized that alcohol enhances susceptibility to opportunistic microbes. The review covers recent studies of the effects of these drugs on immunity and on increased susceptibility to infectious diseases, including AIDS.

Microbial Infections, Immunomodulation, and Drugs of Abuse

BackgroundOpioids are used by patients who have conditions ranging from the acute pain of surgery and chronic cancer pain to substance abuse. Despite their widespread use and considerable experimental data about them, little is known about how opioids may alter in vivo immunity in humans. This study

Morphine Inhibits Spontaneous and Cytokine-enhanced Natural Killer Cell Cytotoxicity in Volunteers

Morphine was demonstrated to exacerbate infections. Experiments were performed to evaluate variations of phagocytic physiology during morphine treatment. In mice, morphine drastically reduced reticuloendothelial system activity, phagocyte count, phagocytic index, killing properties, and superoxide anion production in polymorphonuclear leukocytes and macrophages. Similar effects on alveolar macrophage count, phagocytosis, and killing were found in rabbits, a result which suggested a lack of species specificity. Additional experiments demonstrated that morphine (1) induces a reduction of lymphoid organ weight, (2) impairs the ability to eradicate infections and (3) is counteracted in its depressing activity on phagocytic physiology by small amounts of Corynebacterium parvum. The results suggest that there is a close relationship between the fact that morphine exacerbates infections and the fact that morphine depresses phagocytic functions; therefore, the negative effect of morphine on phagocytosis is at least one of the reasons for its negative effect on the development of infections.

Giorgio Borelli

Papers

Effect of morphine on resistance to infection.

Morphine and methadone impact on human phagocytic physiology

Liver xanthine oxidase increase in mice in three patholgoical models. A possible defence mechanism.

Methadone vs morphine: comparison of their effect on phagocytic functions.

Antiplatelet effects of a new de-N-acetyl-lyso-glycosphingolipid