PMID- 7856754 OWN - NLM STAT- MEDLINE DCOM- 19950316 LR - 20181113 IS - 0002-9440 (Print) IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 146 IP - 2 DP - 1995 Feb TI - Regulatory roles of tumor necrosis factor-alpha and interleukin-1 beta in monocyte chemoattractant protein-1-mediated pulmonary granuloma formation in the rat. PG - 450-62 AB - Intravenous infusion of particulate yeast cell wall glucan into rats results in the synchronous development of angiocentric pulmonary granulomas that are composed almost entirely of monocytes and macrophages. Previous studies indicate that locally produced monocyte chemoattractant protein-1 (MCP-1) is required for full granuloma development. Because tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 (IL-1) can induce MCP-1 production in a variety of cell types, we sought to determine their potential regulatory roles in this model. A single infusion of anti-TNF-alpha antibody at the time of glucan infusion (time 0) markedly reduced MCP-1 mRNA levels at 1 and 6 hours but not at later time points; there was no effect on granuloma size or number measured at 48 hours. When multiple infusions of anti-TNF-alpha antibody were administered over a 23-hour period (0 to 23 hours), MCP-1 mRNA was reduced through 24 hours, there was a significant reduction in peak bronchoalveolar lavage fluid MCP-1 activity at 48 hours, and there were marked reductions in granuloma size and number at 48 hours. Similar results were observed in animals that received infusions of anti-IL-1 beta. Infusion of anti-IL-1 beta at time 0 resulted in moderate reductions in MCP-1 mRNA at 1 and 6 hours and had no effect on granuloma size or number measured at 48 hours. When multiple infusions of anti-IL-1 beta were administered over a 23-hour period (0 to 23 hours), MCP-1 mRNA was reduced through 24 hours, there was a moderate reduction in peak bronchoalveolar lavage fluid MCP-1 activity at 48 hours, and there were marked reductions in granuloma size and number at 48 hours. A single infusion of anti-TNF-alpha and anti-IL-1 beta together at time 0 resulted in marked reductions in whole lung MCP-1 and mRNA at 1 and 6 hours, but not at 24 hours. Multiple combined infusions of anti-TNF-alpha and anti-IL-1 beta over a 23-hour period resulted in additive reductions in MCP-1 mRNA through 24 hours, bronchoalveolar lavage fluid MCP-1 activity at 48 hours, and granuloma size and number at 48 hours. These data suggest that locally produced TNF-alpha and IL-1 beta play regulatory roles in glucan-induced pulmonary granulomatous vasculitis through the modulation of local MCP-1 production. FAU - Flory, C M AU - Flory CM AD - Pharmaceutical Research Division, Warner Lambert-Parke Davis, Ann Arbor, Michigan. FAU - Jones, M L AU - Jones ML FAU - Miller, B F AU - Miller BF FAU - Warren, J S AU - Warren JS LA - eng GR - 5T 32-HL07517/HL/NHLBI NIH HHS/United States GR - HL48287/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Antibodies) RN - 0 (Chemokine CCL2) RN - 0 (Chemotactic Factors) RN - 0 (Glucans) RN - 0 (Interleukin-1) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Antibodies/*pharmacology MH - Bronchoalveolar Lavage Fluid MH - Chemokine CCL2 MH - Chemotactic Factors/*metabolism MH - Glucans MH - Granuloma/chemically induced/*metabolism/pathology MH - Interleukin-1/metabolism/*pharmacology MH - Lung/metabolism MH - Lung Diseases/chemically induced/*metabolism/pathology MH - Male MH - RNA, Messenger/metabolism MH - Rats MH - Specific Pathogen-Free Organisms MH - Time Factors MH - Tumor Necrosis Factor-alpha/metabolism/*pharmacology PMC - PMC1869859 EDAT- 1995/02/01 00:00 MHDA- 1995/02/01 00:01 PMCR- 1995/08/01 CRDT- 1995/02/01 00:00 PHST- 1995/02/01 00:00 [pubmed] PHST- 1995/02/01 00:01 [medline] PHST- 1995/02/01 00:00 [entrez] PHST- 1995/08/01 00:00 [pmc-release] PST - ppublish SO - Am J Pathol. 1995 Feb;146(2):450-62.