Association of Clara cell 10-kDa protein, spontaneous regression and sarcoidosis

Sarcoidosis is a systemic granulomatous disorder with a high rate of sponta neous regression. Clara cell 10-kDa protein (CC10), the predominant product of nonciliated bronchiolar epithelial cells, is a potent immunoregulatory and antiinflammatory agent, CC10 levels were measured in sera and bronchoalveolar lavage (BAL) fluids f rom 31 sarcoidosis patients (nine progressive disease and 22 regressive dis ease) and their relevance to spontaneous regression investigated. The inhib itory effects of recombinant CC10 on interferon gamma (IFN-gamma) productio n were examined using lipopolysaccharide (LPS)-stimulated sarcoid BAL fluid cells, and the blocking effects of monoclonal antibody TY-5, directed agai nst CC10, on CC10 function were also tested. Serum and BAL fluid CC10 levels in the regressive disease group were signif icantly higher than those in the progressive disease group (serum, p<0.05; BAL fluid, p<0.005) and healthy subjects (serum, p<0.0001; BAL fluid, p<0.0 05). CC10 inhibited, in part, IFN-gamma production from LPS-stimulated sarc oid BAL fluid cells (CC10 inhibition: 1,000 ng.mL(-1), 30%; 100 ng.mL(-1), 14%), TY-5 restored IFN-gamma production by blocking CC10 function. Sarcoidosis patients with regressive disease showed increased Clara cell 10 -kDa protein levels in their sera and bronchoalveolar lavage fluids. Clara cell. 10-kDa protein may be a regulator of the inflammatory process in sarc oidosis.