RELEASE OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR BY HUMAN CULTURED AIRWAY SMOOTH-MUSCLE CELLS - SUPPRESSION BY DEXAMETHASONE

Smooth muscle cells represent a significant percentage of the total ce lls in the airway but their contribution to the inflammatory response seen in airway disease has not been studied. Hence, we have looked at the release of the cytokine granulocyte-macrophage colony stimulating factor (GM-CSF) in response to bacterial lipopolysaccharide (LPS) and the pro-inflammatory cytokines interleukin-1 beta (IL-1 beta), tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma). Hu man airway smooth muscle (HASM) cells released GM-CSF under basal cond itions (45.4+/-13.1 pg ml(-1)) that was significantly enhanced by IL-1 beta and TNF alpha with a maximal effect seen at 10 ng ml(-1) (1.31+/ -0.07 ng ml(-1) and 0.72+/-0.16 ng ml(-1), respectively). In contrast, neither LPS nor IFN gamma produced a significant increase in GM-CSF r elease. However, HASM cells exposed to IL-1 beta, TNF alpha and IFN ga mma generated more GM-CSF than that evoked by any cytokine alone (2.2/-0.15 ng ml(-1)). The release of GM-CSF elicited by the cytokine mixt ure was inhibited by cycloheximide and dexamethasone. These data sugge st that HASM cells might play an active part in initiating and/or perp etuating airway inflammation in addition to controlling airway calibre .