INTERLEUKIN-1 RECEPTOR ANTAGONIST EXPRESSION IN SARCOIDOSIS

Sarcoidosis is a systemic granulomatous disease with a marked propensi ty for involvement of the pulmonary parenchyma and thoracic lymphatic system. This granulomatous process is characterized by aggregations of mononuclear cells, multinucleated giant cells, and variable degrees o f fibrosis. The agent(s) responsible for the initiation of the inflamm atory granulomatous process remain unknown. Interleukin-1 beta (IL-1) is a cytokine that has been shown to possess potent proinflammatory pr operties and is likely to play a role in mediating many of the immunop athologic events observed in sarcoidosis. Despite the degree of granul omatous inflammation, both the pulmonary and systemic pathogenic chang es associated with sarcoidosis have a remarkable propensity for sponta neous resolution. The interleukin-1 receptor antagonist (IRAP), an end ogenous inhibitor of IL-1 bioactivity, may have a critical role as an in vivo immunomodulator of IL-1-dependent granulomatous inflammation o f sarcoidosis. In this study we demonstrate constitutive expression of IRAP mRNA and antigen from bronchoalveolar ravage fluid cells and cel l-free fluid, respectively, obtained from both normal subjects and pat ients with sarcoidosis. However, immunolocalization of IRAP was found to be significantly localized to the sarcoid granuloma as compared wit h the uninvolved lung interstitium. Our findings indicate that IRAP ex pression is compartmentalized (granuloma) within the interstitium of p atients with sarcoidosis. Thus, IRAP may function as an important in v ivo immunomodulator of granulomatous inflammation.