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-␣ (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.

Hypothesis: Could Epstein‐Barr virus play a role in the development of gastroschisis?

“…Cigarette smoking, illicit drug use, and stress each negatively affect immune function (Connor, 2004;Godbout and Glaser, 2006;Irwin et al, 2007;Edwards, 2009). If these exposures have cumulative effects on immunity, then older exposed women might be more vulnerable to EBV reactivation than their younger counterparts.…”

Dissociable role of tumor necrosis factor alpha gene deletion in methamphetamine self-administration and cue-induced relapsing behavior in mice

“…In human opiate addicts, the level of TNF-α expression in the brain (locus coeruleus) is higher than that in control subjects (Dyuizen and Lamash 2009). Levels of circulating TNF-α are altered in alcoholics, opiate addicts, and cocaine or marijuana abusers (Baldwin et al 1997;Peng et al 1999;Irwin et al 2007Irwin et al , 2009Gonzalez-Quintela et al 2008;Sacerdote et al 2008;Li et al 2009;Franchi et al 2010), and TNF-α may be a candidate biomarker of alcohol abuse and alcoholism (Achur et al 2010). In our study in animal, TNF-α (−/−) mice were more sensitive to METH self-administration and had a higher motivation for getting METH than wild-type mice.…”

“…Yet reports of the level of circulating TNF-α in human alcoholics, opiate addicts, and cocaine or marijuana abusers are not consistent. Some reports show that the level increases (Gonzalez-Quintela et al 2008;Peng et al 1999;Irwin et al 2009), and others show that the level decreases or does not change (Baldwin et al 1997;Irwin et al 2007;Sacerdote et al 2008;Li et al 2009;Franchi et al 2010). In animals, repeated administration of psychostimulants or opiates induced TNF-α production in the brain or immune system (Friedman and Eisenstein 2004;Nakajima et al 2004;Niwa et al 2007a; Kubera et al 2008).…”

Imaging Biomarkers of the Neuroimmune System among Substance Use Disorders: A Systematic Review

“…Postmortem data indicate long-term cocaine use is associated with 2- to 4-fold higher activated microglia levels relative to controls [184], consistent with MRS findings. Conversely, clinical studies indicate cocaine users exhibit lower systemic proinflammatory cytokine levels than controls [185, 186]. Finally, it is intriguing to speculate that route of administration may modulate cocaine’s effect on the immune system.…”