Differential effects of cigarette smoke constituents on pro‐inflammatory dendritic cell functions

Dendritic cells (DC) are key regulators of immunity. Chronic obstructive pulmonary disease [COPD], a destructive lung disease that affects smokers, is associated with chronic airway inflammation. Although increased DC numbers are found in COPD airways, their functional roles in the pathogenesis of COPD are not well‐defined. We postulated that DCs activated by cigarette smoke constituents directly promote chronic airway inflammation. Concordant with this hypothesis, we observed that incubation of DCs with cigarette smoke extract [CSE], and chronic exposure of mice to cigarette smoke, both augmented the generation of neutrophilic chemokines by immature and lipopolysaccharide [LPS] or CD40L‐matured DCs. The generation of IL‐8 by human DCs conditioned with CSE was completely suppressed by the anti‐oxidant n‐acetyl cysteine [NAC]. Cigarette smoke extract and nicotine augmented the production of secreted prostaglandin‐E2 and intracellular cyclo‐oxygenase‐2 in maturing DCs. Whereas the production of IL‐8 by CSE‐conditioned DCs was suppressed by anti‐oxidants, PGE2 production was augmented by anti‐oxidants, and suppressed by inhibitors of nicotinic signaling. These studies indicate that certain pharmacologic strategies such as anti‐oxidant therapy may be only partially effective in mitigating pro‐inflammatory DC‐mediated responses in smokers. Supported by FARMRI research grant to RV.