Opioids suppress chemokine-mediated migration of monkey neutrophils and monocytes - an instant response

Opioid users having acquired human immunodeficiency syndrome (AIDS) are at a greater risk than non-users of contracting opportunistic infections. Opio id-administered and simian immunodeficiency virus (SIV)-infected rhesus mon keys have been an excellent model for studying AIDS and drug abuse in human s. In this study, chemotaxis of monkey leukocytes was evaluated using the c hemokines interleukin-8 (IL-8) and regulated upon activation, normal T cell expressed (RANTES) as the chemoattractants, and the effects of various opi oid agonists and antagonists on the efficiency of chemotaxis were examined. Opioids were either incubated with monkey leukocytes or added directly to chemokines, and the number of cells migrating toward IL-8 (for neutrophils) or RANTES (for monocytes) was scored. Inhibition of chemotaxis was seen wi th both assay conditions, and the inhibition was mediated by opioids bindin g to mu or kappa receptors. Binding to delta opiod receptors was rarely, if ever, observed. Although opioids themselves may act as weak chemoattractan ts for monkey leukocytes, addition of opioid agonists to chemokines would r educe the chemoattractant ability of the chemokines. Opioids did not cause the same inhibitory effect on the chemotactic migration of neutrophils when the complement component C5a or the chemotactic peptide N-formyl-MET-LEU-P HE (fMLP) was used as chemoattractant. These studies suggest that the prese nce of opioids during SIV infection immediately alters cheomkine-mediated i mmune functions. (C) 2000 Elsevier Science B.V. All rights reserved.