Heroin Use Is Associated with Suppressed Pro-Inflammatory Cytokine Response after LPS Exposure in HIV-Infected Individuals

Abstract

BackgroundOpioid use is associated with increased incidence of infectious diseases. Although experimental studies have shown that opioids affect various functions of immune cells, only limited data are available from human studies. Drug use is an important risk factor for HIV transmission; however no data are available whether heroin and/or methadone modulate immune response. Therefore, we examined the effect of heroin and methadone use among HIV-infected individuals on the production of cytokines after ex vivo stimulation with various pathogens.MethodsTreatment naïve HIV-infected individuals from Indonesia were recruited. Several cohorts of individuals were recruited: 1) using heroin 2) receiving methadone opioid substitution 3) using heroin over 1 year ago and 4) controls (never used opioids). Whole blood was stimulated with Mycobacterium tuberculosis, Candida albicans and LPS for 24 to 48 hours. Cytokine production (IL-1 β, IL-6, IL-10, IFN-α, IFN-γ and TNF-α) was determined using multiplex beads assay.ResultsAmong 82 individuals, the cytokine levels in unstimulated samples did not differ between groups. Overall, heroin users had significantly lower cytokine response after exposure to LPS (p<0.05). After stimulation with either M. tuberculosis or C. albicans the cytokine production of all groups were comparable.ConclusionThe cytokine production after exposure to LPS is significantly down-regulated in HIV-infected heroin users. Interesting, methadone use did not suppress cytokine response, which could have implications guidelines of opioid substitution.

Do All Opioid Drugs Share the Same Immunomodulatory Properties? A Review From Animal and Human Studies

“…Moreover, a controlled methadone or buprenorphine therapy also normalized the Th1/Th2 balance that was significantly unbalanced during chronic heroin use (41). The beneficial effect of methadone maintenance on immune system responses of heroin abusers has been consistently reported also more recently (42)(43)(44). Participation in methadone maintenance treatment was protective against hepatitis C incidence among illicit drug users and methadone exerted a dose-response protective effect on hepatitis C incidence (42).…”

Unchanged Levels of Soluble CD14 and IL-6 Over Time Predict Serious Non-AIDS Events in HIV-1-Infected People

“…12 Data are conflicting on whether cocaine and/or heroin increase sCD14 and IL-6 levels in persons with or without HIV infection. [13][14][15][16][17] The effects of illicit substances on inflammatory markers in HIV-1-infected persons on ART are unknown. Regardless, these data suggest that aggressive drug rehabilitation may be an additional intervention to lower SNAE risk in HIV-1-infected persons.…”

Neuroimmune mechanisms of psychostimulant and opioid use disorders

“…Yet, when opioids are administered concurrently or before toxin exposure, they act to dampen immune cell activation. Cells from heroin abusers have lower levels of pro-inflammatory cytokines such as IL-1b, IL-6, TNF-a, and IFN-c after in vitro stimulation with the bacterial endotoxin lipopolysaccharide (LPS; Meijerink et al, 2015). Similarly, serum from chronic heroin users produced less IFN-c and more IL-10 than healthy controls when stimulated with LPS (Azarang et al, 2007).…”

“…In conclusion, opioids influence inflammation and immune reactivity in a variety of ways that are purported to affect opioid-related behaviors. Some of these factors include upregulation of pro-inflammatory cytokines after short-or prolonged opioid exposure (Hutchinson et al, 2008a), enhanced activation of microglia (Zhang et al, 2011;Fukagawa et al, 2013), reduction in the immune response to pathogens (Azarang et al, 2007;Meijerink et al, 2015), and disruption of intestinal permeability leading to systemic bacterial spread (Meng et al, 2015). The increase in pro-inflammatory cytokines and enhanced activation of microglia resulting from opioid intake most likely contribute to the negative consequences of opioid use, such as tolerance (Johnston et al, 2004;Shavit et al, 2005), dependence (Bland et al, 2009;Hutchinson et al, 2009), and reward (Hutchinson et al, 2008b;Zhang et al, 2012), although the exact cellular mechanisms have yet to be elucidated.…”