Alcohol and cannabis use alter pulmonary innate immunity

Purpose: Cannabis use is increasing due to recent legislative changes. In addition, cannabis is often used in conjunction with alcohol. The airway epithelium is the first line of defense against infectious microbes. Toll-like receptors CUR) recognize airborne microbes and initiate the inflammatory cytokine response. The mechanism by which cannabis use in conjunction with alcohol affects pulmonary innate immunity mediated by TLRs is unknown. Methods: Samples and data from an existing cohort of individuals with alcohol use disorders (AUDs), along with samples from additional participants with cannabis use alone and with AUD were utilized. Subjects were categorized into the following groups: no alcohol use disorder (AUD) or cannabis use (control) (n = 46), AUD only (n = 29), cannabis use-only (n = 39), and AUD and cannabis use (n = 29). The participants underwent bronchoscopy with bronchoalveolar lavage (BAL) and airway epithelial brushings. We measured IL-6, IL-8, TNF alpha, and IL-10 levels in BAL fluid, and performed real-time PCR for TLR1-9 on the airway epithelial brushings. Results: We found significant increases in TLR2 with AUD alone, cannabis use alone, and cannabis use with AUD, compared to control. TLR5 was increased in cannabis users compared to control, TLR6 was increased in cannabis users and cannabis users with AUD compared to control, TLR7 was increased in cannabis users compared to control, and TLR9 was increased in cannabis users compared to control. In terms of cytokine production, IL-6 was increased in cannabis users compared to control. IL-8 and IL-10 were increased in AUD only. Conclusions: AUD and cannabis use have complex effects on pulmonary innate immunity that promote airway inflammation. (C) 2018 Elsevier Inc. All rights reserved.