The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
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Cigarette smoke (CS), the primary risk factor of chronic obstructive pulmonary disease (COPD), leads to pulmonary inflammation through interleukin-1 receptor (IL-1R)I signalling, as determined using COPD mouse models. It is unclear whether interleukin (IL)-1α or IL-1β, activated by the Nlrp3/caspase-1 axis, is the predominant ligand for IL-1RI in CS-induced responses. We exposed wild-type mice (treated with anti-IL-1α or anti-IL-1β antibodies), and IL-1RI knockout (KO), Nlrp3 KO and caspase-1 KO mice to CS for 3 days or 4 weeks and evaluated pulmonary inflammation. ⋯ Interestingly, CS-induced inflammation occurred independently of IL-1β activation by the Nlrp3/caspase-1 axis. In human subjects, IL-1α and IL-1β were significantly increased in total lung tissue and induced sputum of patients with COPD, respectively, compared with never-smokers. These results suggest that not only IL-1β but also IL-1α should be considered as an important mediator in CS-induced inflammation and COPD.