EFFECT OF SLOW-RELEASE IL-12 AND IL-10 ON INFLAMMATION, LOCAL MACROPHAGE FUNCTION AND THE REGIONAL LYMPHOID RESPONSE DURING MYCOBACTERIAL (TH1) AND SCHISTOSOMAL (TH2) ANTIGEN-ELICITED PULMONARY GRANULOMA-FORMATION

Objective and Design: This study examines the local and regional effec ts of exogenously administered interleukins 10 (IL-10) and 12 (IL-12) on pulmonary granulomas mediated by Th1/type 1-(IFN-gamma) and Th2/typ e 2-(IL-4, IL-5) cytokines. Materials and Treatments: Granulomas (GR) were induced in presensitized CBA mice by embolization of beads coated with Mycobacteria tuberculosis or Schistosoma mansoni egg antigens. B efore challenge, osmotic pumps distributing IL-10 or IL-12 (50 mu g/kg /day) were implanted intraperitoneally, then GR and draining lymph nod es were examined 4 days. Methods: GR sizes and composition were determ ined by morphometry and differential analysis. Isolated GR macrophages and draining lymph nodes were assessed for cytokine production by ELI SA. Results: IL-10 did not effect GR sizes but reduced neutrophils in type 1 GR. IL-12 minimally reduced type 1 GR but decreased the type 2 lesion by up to 70%, primarily curtailing eosinophils. Type 2 GR macro phages were unaffected but type 1 were impaired by IL-10. Conversely, type 1 GR macrophages were more resistant to IL-12 while type 2 showed enhanced IL-10, IL-12 and TNF, but reduced MCP-1 production. In lymph nodes, IL-10 caused paradoxical effects, enhancing IFN-gamma in the t ype 1 and decreasing Th2 cytokines in the type 2 response. Exogenous I L-12 profoundly augmented IFN-gamma and abrogated type 2 cytokines whi le inhibiting intrinsic IL-12 production in lymph nodes. Conclusion: T hese findings provide novel information regarding cytokine regulation and the effects of systemic cytokine therapy.