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.

Crack cocaine addiction, early life stress and accelerated cellular aging among women

“…Long-term cocaine use contributes to important health problems, including coronary artery disease (Degenhardt et al, 2011), major depressive disorder (Herrero, Domingo-Salvany, Torrens, Brugal, & Investigators, 2008), cognitive decline (Verdejo-Garcia, Perez-Garcia, Sanchez-Barrera, Rodriguez-Fernandez, & Gomez-Rio, 2007;Viola et al, 2015), and. In addition, cocaine use has been associated with increased peripheral inflammatory mediators (Araos et al, 2015;Fox et al, 2012;Levandowski et al, 2014) and age-related atrophy in grey matter volume (Ersche, Jones, Williams, Robbins, & Bullmore, 2013) both of which are commonly seen in association with aging and age-related disorders (Sander et al, 2008).…”

Vascular disease in cocaine addiction

“…Cocaine creates an elevated immune system inflammatory state with decreased basal anti-inflammatory markers (e.g., interleukin-10) [42,51], and increased pro-inflammatory cytokines (e.g., tumor necrosis factor alpha, Interleukin 1β) [42,51], all contributing to vascular disease (e.g., endocarditis).…”

“…Medication to reduce inflammation (e.g., recombinant IL-10, soluble receptor medication such as Etanercept) may be helpful to control cocaine induced inflammatory cascade [51]. As nitric oxide/glyceraldehyde-3-phosphate dehydrogenase pathway mediates cocaine induced autophagy, glyceraldehyde-3-phosphate dehydrogenase can be tested for use (see clinical trials in Parkinson's disease [48,94]).…”

Descripción de los hallazgos en el perfil lipídico y proteico de pacientes dependientes a cocaína, en abstinencia reciente

“…Drogas que producen adicción presentarían efectos inmunomodulatorios con alteraciones de interleukina 6 (IL-6) en saliva y elevación de factor de necrosis tumoral (TNF-alfa) pro-inflamatorio, frente a estrés por estímulo con imágenes de disgusto 28,29 . Las citoquinas pro-inflamatorias, marcadores de riesgo metabólico y de aterosclerosis, también favorecerían la mayor frecuencia de estos problemas en adictos.…”