Immune system inflammation in cocaine dependent individuals: implications for medications development

Abstract

Objectives: Cocaine dependence is a chronic stress state. Furthermore, both stress and substance abuse have robust and reciprocal effects on immune system cytokines, which are known to be powerful modulators of mood. We therefore examine basal and provoked changes in peripheral cytokines in cocaine dependent individuals to better understand their role in the negative reinforcing effects of cocaine.

Methods: Twenty-eight (16 F/12 M) treatment-seeking cocaine dependent individuals and 27 (14 F/13 M) social drinkers were exposed to three 5-min guided imagery conditions (stress, drug cue, relaxing) presented randomly across consecutive days. Measures of salivary cortisol, tumor necrosis factor alpha (TNFα), interleukin-10 (IL-10), and interleukin-1 receptor antagonist (IL-1ra) were collected at baseline and various post-imagery time-points.

Results: Cocaine abusers demonstrated decreased basal IL-10 compared with social drinkers. They also showed significant elevations in pro-inflammatory TNFα when exposed to stress compared with when they were exposed to relaxing imagery. This was not observed in the social drinkers. Conversely, social drinkers demonstrated increases in the anti-inflammatory markers, IL-10 and IL-1ra, following exposure to cue, which were not seen in the dependent individuals.

Conclusions: Cocaine dependent individuals demonstrate an elevated inflammatory state both at baseline and following exposure to the stress imagery condition. Cytokines may reflect potentially novel biomarkers in addicted populations for treatment development.

Figure 1

Overview of study schedules for (a) socially drinking controls and (b) cocaine dependent individuals

Figure 2

Laboratory schedule (identical for all 3 days, with the exception of the imagery condition presented)

Figure 3

Group differences between cocaine dependent individuals and social drinkers in basal levels of Interleukin-10

Figure 4

Group differences between cocaine dependent individuals and social drinkers in (a) TNF alpha, (b) Interleukin-10, and (c) Interleukin-1 receptor antagonist following exposure to stress-related and cue-related imagery. Bars represent response in these conditions relative to the relaxing (control) imagery condition (means and standard errors shown). As no significant time-point interactions were observed, bars represent data collapsed across all time-points.