Cocaine dependence and acute cocaine induce decreases of monocyte proinflammatory cytokine expression across the diurnal period: autonomic mechanisms.

TitleCocaine dependence and acute cocaine induce decreases of monocyte proinflammatory cytokine expression across the diurnal period: autonomic mechanisms.
Publication TypeJournal Article
Year of Publication2007
AuthorsIrwin MR, Olmos L, Wang M, Valladares EM, Motivala SJ, Fong T, Newton T, Butch A, Olmstead R, Cole SW
JournalJ Pharmacol Exp Ther
Volume320
Issue2
Pagination507-15
Date Published2007 Feb
ISSN0022-3565
KeywordsAdult, Autonomic Nervous System, Cocaine, Cocaine-Related Disorders, Cytokines, HIV Infections, Humans, Immunity, Innate, Interleukin-6, Lipopolysaccharides, Middle Aged, Monocytes, Receptors, Tumor Necrosis Factor, Type II, Time Factors, Tumor Necrosis Factor-alpha
Abstract

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-alpha (TNF-alpha) 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-alpha 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-alpha and IL-6 were profiled over 48 h. Cocaine-dependent volunteers showed a decrease in the capacity of monocytes to express TNF-alpha 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-alpha. 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.

DOI10.1124/jpet.106.112797
Alternate JournalJ. Pharmacol. Exp. Ther.
PubMed ID17068203
Grant ListAA13239 / AA / NIAAA NIH HHS / United States
DA16541 / DA / NIDA NIH HHS / United States
M01 RR00827 / RR / NCRR NIH HHS / United States
T32-MH19925 / MH / NIMH NIH HHS / United States