Cytokine- and virus-stimulated airway smooth muscle cells produce IL-11 and other IL-6-type cytokines

Inflammation and smooth muscle abnormalities coexist in human airway disorders, and inflammation modulates the proliferative and contractile properties of airway smooth muscle cells. To determine whether human airway smooth muscle (HASM) cells have the ability to regulate local inflammatory processes, we characterized the interleukin (IL)-6-type cytokine production of HASM cells in vitro. We demonstrated that HASM cells are potent producers of IL-11 when stimulated with IL-1 or transforming growth factor-beta 1 (TGF-beta 1) and that IL-11 levels are synergistically increased by IL-1 and TGF-beta 1 in combination. These studies also demonstrated that IL-l and TGF-beta 1-stimulated HASM cells produce IL-6 and leukemia inhibitory factor but not oncostatin M and that respiratory syncytial virus and parainfluenza virus type 3 stimulate HASM cell IL-11 production. Finally, they demonstrate that, in all cases, the stimulation of HASM cell IL-11 elaboration is pretranslationally mediated since cytokine- and virus-induced alterations in IL-11 protein production were associated with proportionate changes in IL-11 mRNA accumulation. HASM cells are potent producers of IL-ll and other IL-6-type cytokines and may be important regulators of local airway inflammation.