Cigarette Smoke Constituents and Nicotine Differentially Affect Cytokine Production by Human Macrophages Stimulated by TLR Ligands : Considerations for a Standardised Protocol.

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung condition associated with cigarette (tobacco) smoking. Numerous animal studies have been conducted to investigate the links between cigarette smoke, nicotine and infection in lung pathology. As an alternative to animal experiments, we used an system to investigate the effects of cigarette smoke extract (CSE) or nicotine on TNF-α and IL-10 production by monocyte-derived human macrophages. The macrophages were simultaneously stimulated with either poly-IC (as a chemical surrogate for viral infection) or lipopolysaccharide (as a chemical surrogate for Gram-negative bacterial infection). CSE enhanced TNF-α production, whereas nicotine inhibited IL-10 production by the macrophages, particularly when co-stimulated with the microbial chemical surrogates. A system of this type may help to further our understanding of the immunological and inflammatory effects of smoking, without recourse to studies. Requirements for the optimisation and standardisation of such an system are also discussed.