PMID- 9098720 OWN - NLM STAT- MEDLINE DCOM- 19970619 LR - 20031114 IS - 1023-3830 (Print) IS - 1023-3830 (Linking) VI - 46 IP - 3 DP - 1997 Mar TI - 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. PG - 86-92 AB - 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 micrograms/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 GR macrophages were more resistant to IL-12 while type 2 showed enhanced IL-10, IL-12 and TNF, but reduced MCP-I 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. FAU - Chensue, S W AU - Chensue SW AD - Department of Pathology and Laboratory Medicine, Veterans Affairs Medical Center, Ann Arbor, MI 48105, USA. FAU - Warmington, K AU - Warmington K FAU - Ruth, J H AU - Ruth JH FAU - Kunkel, S L AU - Kunkel SL LA - eng PT - Journal Article PL - Switzerland TA - Inflamm Res JT - Inflammation research : official journal of the European Histamine Research Society ... [et al.] JID - 9508160 RN - 0 (Antigens, Bacterial) RN - 0 (Antigens, Helminth) RN - 0 (Delayed-Action Preparations) RN - 130068-27-8 (Interleukin-10) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Animals MH - Antigens, Bacterial/immunology MH - Antigens, Helminth/immunology MH - Delayed-Action Preparations MH - Female MH - Granuloma/*drug therapy/immunology/pathology MH - Inflammation/*drug therapy/immunology MH - Interleukin-10/*therapeutic use MH - Interleukin-12/*therapeutic use MH - Lung Diseases/*drug therapy/immunology/pathology MH - Lymph Nodes/drug effects/immunology MH - Macrophages, Alveolar/*drug effects/immunology MH - Mice MH - Mice, Inbred CBA MH - Mycobacterium tuberculosis/immunology MH - Schistosoma mansoni/immunology MH - Th1 Cells/immunology MH - Th2 Cells/immunology EDAT- 1997/03/01 00:00 MHDA- 1997/03/01 00:01 CRDT- 1997/03/01 00:00 PHST- 1997/03/01 00:00 [pubmed] PHST- 1997/03/01 00:01 [medline] PHST- 1997/03/01 00:00 [entrez] AID - 10.1007/s000110050101 [pii] AID - 10.1007/s000110050101 [doi] PST - ppublish SO - Inflamm Res. 1997 Mar;46(3):86-92. doi: 10.1007/s000110050101.