Antiinflammatory effect of retrovirally transfected interleukin‐10 on monosodium urate monohydrate crystal–induced acute inflammation in murine air pouches

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Abstract
Objective: To investigate the role of interleukin‐10 (IL‐10) in the inflammatory response, the antiinflammatory effect of retrovirally transfected IL‐10 was evaluated both in vitro and in vivo.Methods: A recombinant retrovirus containing the murine IL‐10 gene was constructed using the pLXSN vector and was designated as LXSN‐IL‐10. Murine IL‐10 was introduced into embryonic C57BL/6J fibroblast cells using LXSN‐IL‐10 to create C57‐IL‐10 cells. The effect of IL‐10 in the culture supernatant of these cells was then evaluated by determining changes in the production of tumor necrosis factor α (TNFα), macrophage inflammatory protein 1α (MIP‐1α), and MIP‐1β by macrophages. The antiinflammatory effect of C57‐IL‐10 cells was also investigated using an in vivo model of monosodium urate monohydrate (MSU) crystal–induced acute inflammation.Results: The IL‐10 gene transcript and its product were detected by reverse transcriptase–polymerase chain reaction and enzyme‐linked immunosorbent assay, respectively. The level of IL‐10 in the culture supernatant of C57‐IL‐10 cells was estimated to be 50 ng/ml. The culture supernatant of these cells exerted the biologic activity of IL‐10, showing inhibition of TNFα, MIP‐1α, and MIP‐1β production by macrophages. Injection of C57‐IL‐10 cells into murine air pouches significantly inhibited MSU crystal–induced cellular infiltration (P < 0.01) and production of the mouse CXC chemokine KC (P < 0.05). These findings were consistent with the results obtained by the injection of recombinant human IL‐10 into air pouches.Conclusion: In this murine air pouch model of MSU crystal–induced inflammation, IL‐10 seemed to inhibit the recruitment of neutrophils at least partly by suppressing KC production. These findings seem to suggest that IL‐10 gene therapy may be useful for inflammatory diseases.

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