PMID- 9714185 OWN - NLM STAT- MEDLINE DCOM- 19980831 LR - 20131121 IS - 0023-6837 (Print) IS - 0023-6837 (Linking) VI - 78 IP - 8 DP - 1998 Aug TI - Production and regulation of monocyte chemoattractant protein-1 in lipopolysaccharide- or monosodium urate crystal-induced arthritis in rabbits: roles of tumor necrosis factor alpha, interleukin-1, and interleukin-8. PG - 973-85 AB - The production of monocyte chemoattractant protein-1 (MCP-1) and its regulation by TNFalpha, IL-1, and IL-8 were investigated in two rabbit models of arthritis induced by intra-articular injection of lipopolysaccharide (LPS) or monosodium urate (MSU) crystals. We first prepared recombinant rabbit MCP-1 and antibodies and then developed an immunoassay. The immunoassay detected 3 pg/ml rabbit MCP-1 and did not cross-react with other rabbit chemokines such as IL-8 or GRO. MCP-1 was first detected in synovial fluid (SF) at 1 hour, and peaked at 4 or 2 hours after the injection of LPS or MSU crystals, respectively. Immunohistochemically, MCP-1 was detected in synovial lining cells and infiltrating neutrophils. The amounts of MCP-1 detected in SF from neutrophil-depleted rabbits were similar to those in normal rabbits, suggesting that synovial lining cells were the main source of MCP-1 detected in SF. The peak level of MCP-1 in SF after LPS-injection was inhibited by 57% with anti-TNFalpha mAb and by 41% with IL-1 receptor antagonist (IL-1Ra). Coadministration of anti-TNFalpha mAb and IL-1Ra inhibited 90% of MCP-1 production. In contrast, the peak level of MCP-1 in SF after MSU crystal-injection was not affected by any cytokine inhibitor, but was reduced by 52% with coadministration of anti-TNFalpha mAb and IL-1Ra. Anti-IL-8 IgG had no effect on the production of MCP-1 in either model. Thus, the production of MCP-1 in LPS-induced arthritis was mostly regulated by TNFalpha and IL-1, whereas half the extent of MCP-1 production in MSU crystal-induced arthritis was independent of TNFalpha or IL-1. IL-8 does not seem to regulate the production of MCP-1 in SF either directly or indirectly. Finally, administration of neutralizing anti-MCP-1 antibody inhibited LPS- and MSU crystal-induced monocyte infiltration by 58.4% and 44.9%, respectively, suggesting that synovial production of MCP-1 plays an important role in the recruitment of monocytes in these arthritis models. FAU - Matsukawa, A AU - Matsukawa A AD - Department of Pathology, Kumamoto University School of Medicine, Honjo, Japan. FAU - Miyazaki, S AU - Miyazaki S FAU - Maeda, T AU - Maeda T FAU - Tanase, S AU - Tanase S FAU - Feng, L AU - Feng L FAU - Ohkawara, S AU - Ohkawara S FAU - Yoshinaga, M AU - Yoshinaga M FAU - Yoshimura, T AU - Yoshimura T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Lab Invest JT - Laboratory investigation; a journal of technical methods and pathology JID - 0376617 RN - 0 (Antibodies, Monoclonal) RN - 0 (Chemokine CCL2) RN - 0 (Immune Sera) RN - 0 (Interleukin-1) RN - 0 (Interleukin-8) RN - 0 (Lipopolysaccharides) RN - 0 (Recombinant Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 268B43MJ25 (Uric Acid) SB - IM MH - Animals MH - Antibodies, Monoclonal/biosynthesis MH - Arthritis/chemically induced/*metabolism/pathology MH - COS Cells MH - Cell Movement/immunology MH - Chemokine CCL2/analysis/*biosynthesis/genetics/immunology MH - Crystallization MH - Female MH - Fluoroimmunoassay MH - Immune Sera/administration & dosage/biosynthesis MH - Injections, Intra-Articular MH - Injections, Intravenous MH - Interleukin-1/*physiology MH - Interleukin-8/*physiology MH - Knee Joint/pathology MH - Lipopolysaccharides/*toxicity MH - Monocytes/pathology MH - Rabbits MH - Recombinant Proteins/analysis/biosynthesis/immunology MH - Synovial Fluid/chemistry MH - Tumor Necrosis Factor-alpha/*physiology MH - Uric Acid/*toxicity EDAT- 1998/08/26 00:00 MHDA- 1998/08/26 00:01 CRDT- 1998/08/26 00:00 PHST- 1998/08/26 00:00 [pubmed] PHST- 1998/08/26 00:01 [medline] PHST- 1998/08/26 00:00 [entrez] PST - ppublish SO - Lab Invest. 1998 Aug;78(8):973-85.