This project will examine the effect of morphine on parameters of immune function in normal macaques ormacaques chronically infected with Simian Immunodeficiency Virus (SIV), the best model for human infectionwith HIV. Peripheral blood mononuclear cells collected before and after SIV infection oropioid treatmentwill be used to assess Natural Killer cell activity, responses to T and B cell mitogens, and levels ofproinflammatory cytokines. The effect of the drug on immune status and SIV viral load will be madelongitudinally in each animal, as well as among animals in a treatment group and between groups. One thirdof HIV infected individuals in the U.S. are intravenous drug abusers. Morphine is the primary activemetabolite of heroin, and is the classic opioid used in most laboratory studies. Morphine is known to beimmunosuppressive in animal models and has been shown to up-regulate HIV replication in vitro. Yet, theeffect of opioid drugs on progression of retroviral infections in vivo has never been definitively established,nor has the effect of opioids on parameters of immune function been evaluated in retrovirally infectedanimals. Natural Killer cell activity, mitogen responses, and cytokine profiles are the standard functional teststhat have been used in the majority of published studies examining effects of opioids on immune status, andtherefore have been chosen for this project. The proposed studies will provide new data on the effects ofchronic treatment with morphine on immune status in uninfected macaques, as well as testing the effects ofchronic morphine in SIV infected animals, on immune status and disease progression, including neurologicalinvolvement. A novel aspect of the proposed studies is that the effect of morphine will be tested on SIVinfection when the drug is given before or after the virus. Also, few studies in any species have examinedthe effects of chronic opioid treatment on immune functional parameters. The data collected in the proposedwork will be novel, and will help to answer the questions directly as to whether opioids affect progression of aretroviral infection in primates, and whether the drug alters functional immune responses.
Showing the most recent 10 out of 18 publications
