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 effects of exogenously administered interleukins 10 (IL-10) and 12 (IL-12) on pulmonary granulomas mediated by Th1/type 1-(IFN-gamma) and Th2/type 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. Before challenge, osmotic pumps distributing IL-10 or IL-12 (50 mu g/kg/day) were implanted intraperitoneally, then GR and draining lymph nodes were examined 4 days. Methods: GR sizes and composition were determined by morphometry and differential analysis. Isolated GR macrophages and draining lymph nodes were assessed for cytokine production by ELISA. 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 macrophages 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 type 1 and decreasing Th2 cytokines in the type 2 response. Exogenous IL-12 profoundly augmented IFN-gamma and abrogated type 2 cytokines while inhibiting intrinsic IL-12 production in lymph nodes. Conclusion: These findings provide novel information regarding cytokine regulation and the effects of systemic cytokine therapy.