Cocaine dependence and acute cocaine induce decreases of monocyte proinflammatory cytokine expression across the diurnal period: autonomic mechanisms.
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.
Irwin
Michael R
MR
Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, CA 90095-7057, USA. mirwin1@ucla.edu
Olmos
Luis
L
Wang
Minge
M
Valladares
Edwin M
EM
Motivala
Sarosh J
SJ
Fong
Tim
T
Newton
Tom
T
Butch
Anthony
A
Olmstead
Richard
R
Cole
Steve W
SW
D000328:Adult; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000097:blood / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D003042:Cocaine