QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.106.112797v1 jpet.106.112797v2 320/2/507    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Irwin, M. R. Articles by Cole, S. W. Search for Related Content PubMed PubMed Citation Articles by Irwin, M. R. Articles by Cole, S. W.

INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Cocaine Dependence and Acute Cocaine Induce Decreases of Monocyte Proinflammatory Cytokine Expression across the Diurnal Period: Autonomic Mechanisms

Cousins Center for Psychoneuroimmunology, University of California, Los Angeles; and Semel Institute for Neuroscience, Los Angeles, California

Cocaine dependence is associated with an increased risk of infectious diseases. The innate immune system triggers effector pathways to combat microbial pathogens through expression of tumor necrosis factor- (TNF-) and interleukin-6 (IL-6). It is not known whether cocaine alters the capacity of monocytes to respond to a bacterial challenge in humans. In cocaine-dependent volunteers and control subjects, we analyzed monocyte TNF- and IL-6 expression at rest and in response to the bacterial ligand, lipopolysaccharide (LPS), over a 24-h period. In addition, the in vivo effects of cocaine (40 mg) versus placebo on monocyte expression of TNF- and IL-6 were profiled over 48 h. Cocaine-dependent volunteers showed a decrease in the capacity of monocytes to express TNF- and IL-6 compared with control subjects. Moreover, acute infusion of cocaine induced a further decline in the responsiveness of monocytes to LPS, which persisted after cocaine had cleared from the blood. Heart rate variability analyses showed that increases of sympathetic activity along with vagal withdrawal were associated with decreases in monocyte expression of TNF-. Cocaine alters autonomic activity and induces protracted decreases in innate immune mechanisms. Targeting sympathovagal balance might represent a novel strategy for partial amelioration of impairments of innate immunity in cocaine dependence.

Address correspondence to: Dr. Michael Irwin, Cousins Center for Psychoneuroimmunology, Los Angeles, CA 90095-7057. E-mail: mirwin1{at}ucla.edu