ENDOGENOUS IL-1 RECEPTOR ANTAGONIST PROTEIN (IRAP) REGULATES SCHISTOSOME EGG GRANULOMA-FORMATION AND THE REGIONAL LYMPHOID RESPONSE

This study examined the role of IL-1 receptor antagonist protein (IRAP ) in the regulation of the immune/inflammatory. response to schistosom e eggs. Initial screening for IRAP-specific mRNA transcripts by revers e transcriptase and primer-directed polymerase chain reactions suggest ed significant endogenous IRAP synthesis in lungs with Schistosoma man soni egg-induced hypersensitivity granulomas but not in normal lungs o r lungs with nonimmune bead granulomas. Direct detection using mIRAP-s pecific antibodies corroborated the RNA studies. Both ELISA and immuno histochemical studies revealed significant spontaneous IRAP production in cultures of isolated egg granulomas and regional reactive lymphoid tissue that could be localized largely but not exclusively to macroph ages. Synchronously developing secondary schistosome egg granulomas sh owed accelerated and augmented IRAP production compared with primary l esions, paralleling granuloma cellularity and growth kinetics. Nonimmu ne T cell-independent bead lesions produced the least amounts of IRAP. In draining lymphoid tissue the onset of IRAP production corresponded with local cell proliferation in both primary and secondary egg respo nses. Next, the in vivo role of IRAP was tested by administration of a nti-IRAP antisera which caused 40-50% increases in egg granuloma area. Moreover, treatment increased (50-1 00%) IL-2, IL-4, IL-1 0, and IFN- gamma production in the primary response and all but IFN in secondary response lymph node cultures. Our results suggest that IRAP is an endo genous regulatory protein and may limit the activity of IL-1 during th e Ag-specific granulomatous response to schistosome eggs. Furthermore, our findings provide in vivo support for the notion that Ag-elicited lymphocyte-derived products probably augment IRAP production and block the action of IL-1.