Fibroblasts play a sentinel role in asthmatic disease. They are the main constituents of connective tissue and are increased in number in the asthmatic lung. They are also capable of secreting a diverse repertoire of cytokines and are able to be activated by pro-inflammatory cytokines and cell-cell contact. Previously we have reported that normal human lung fibroblasts (NHLF) can be activated by monocytes (U937) through cell-cell contact to produce GM-CSF. Here we show that GM-CSF production from NHLF activated by monocyte contact is inhibited by prednisone, a synthetic glucocorticoid used in the treatment of asthma. GM-CSF is an acidic glycoprotein that potentiates development of cells in the granulocyte and macrophage lineage and is secreted at sites of peripheral inflammation. The receptor for GM-CSF was found on NHLF by flow cytometry and was able to be up-regulated by interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha and recombinant human (rh) GM-CSF. To test autocrine effects of GM-CSF on fibroblasts, rh GM-CSF was used in proliferation studies and was found to decrease fibroblast proliferation. Prednisone was used to block NF-kappaB activation and GM-CSF gene expression as well. These data indicate mechanism of action and treatment for cell-cell contact mediated inflammation of infiltrating monocytes with fibroblasts as seen in asthma and other diseases like graft versus host disease.