Received for publication August 22, 2006.
Revised October 24, 2006.
Accepted for publication October 25, 2006.

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

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-) 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 controls, this study analyzed monocyte TNF- and IL-6 expression at rest and in response to the bacterial ligand, lipopolysaccharide (LPS), over a 24-hour period. In addition, the in vivo effects of cocaine (40 mg) vs. placebo on monocyte expression of TNF- and IL-6 were profiled over 48 hours. Cocaine dependent volunteers showed a decrease in the capacity of monocytes to express TNF- and IL-6 as compared to controls. 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.

Key words: autonomic activity, cocaine, cytokines, innate immunity, psychostimulants, sympathetic activity