PT  - JOURNAL ARTICLE
AU  - Michael R. Irwin
AU  - Luis Olmos
AU  - Minge Wang
AU  - Edwin M. Valladares
AU  - Sarosh J. Motivala
AU  - Tim Fong
AU  - Tom Newton
AU  - Anthony Butch
AU  - Richard Olmstead
AU  - Steve W. Cole
TI  - Cocaine Dependence and Acute Cocaine Induce Decreases of Monocyte Proinflammatory Cytokine Expression across the Diurnal Period: Autonomic Mechanisms
AID  - 10.1124/jpet.106.112797
DP  - 2007 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 507--515
VI  - 320
IP  - 2
4099  - http://jpet.aspetjournals.org/content/320/2/507.short
4100  - http://jpet.aspetjournals.org/content/320/2/507.full
SO  - J Pharmacol Exp Ther2007 Feb 01; 320
AB  - 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-α (TNF-α) 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-α 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-α and IL-6 were profiled over 48 h. Cocaine-dependent volunteers showed a decrease in the capacity of monocytes to express TNF-α 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-α. 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. The American Society for Pharmacology and Experimental Therapeutics