Laboratory of Immunobiology, Rega Institute, University of Leuven, Leuven, Belgium.
Eur J Immunol. 2012 Dec;42(12):3223-34. doi: 10.1002/eji.201242573. Epub 2012 Oct 16.
Following immunization with collagen II (CII) in complete Freund's adjuvant (CFA), DBA/1 mice develop arthritis of major joints. This collagen-induced arthritis (CIA) is used as a model for rheumatoid arthritis (RA) in man. Inflammatory changes in lung tissue commonly occur in RA. However, evidence for pulmonary inflammation in CIA is scarce and ambiguous. Here, we demonstrate pulmonary inflammation accompanying CIA in wild-type DBA/1 mice. In IFN-γ receptor-deficient (IFN-γR KO) mice, inflammation was more frequent and more severe. Injection of CFA only (without CII) proved to be as efficient in eliciting pulmonary inflammation as immunization with CFA + CII, though being less effective in causing arthritis. Significant correlation in severity between joint and pulmonary involvement could not be demonstrated. Macroscopic, microscopic, and functional characteristics of pulmonary inflammation in the mice resembled those seen in human RA. Increased inflammation in IFN-γR KO mice was accompanied by augmented expression of various cytokines and chemokines, as measured by RT-PCR on affected tissue. Treatment with a TNF-α inhibitor ameliorated lung pathology. We conclude that CIA in DBA/1 mice is accompanied by pulmonary inflammation. Although both disease processes are kept in check by endogenous IFN-γ, lack of strict parallelism indicates that overlap in their pathogeneses is partial.
在完全弗氏佐剂（CFA）中免疫胶原 II（CII）后，DBA/1 小鼠会发展为大关节关节炎。这种胶原诱导性关节炎（CIA）被用作人类类风湿关节炎（RA）的模型。在 RA 中，肺组织的炎症变化很常见。然而，CIA 中肺炎症的证据很少且存在争议。在这里，我们证明了野生型 DBA/1 小鼠 CIA 伴有肺炎症。在 IFN-γ 受体缺陷（IFN-γR KO）小鼠中，炎症更频繁且更严重。仅注射 CFA（不含 CII）与用 CFA+CII 免疫一样有效地引发肺炎症，尽管在引起关节炎方面效果较差。关节和肺部受累之间的严重程度无明显相关性。小鼠肺部炎症的宏观、微观和功能特征与人类 RA 所见相似。IFN-γR KO 小鼠中炎症的增加伴随着各种细胞因子和趋化因子的表达增加，这可以通过受影响组织的 RT-PCR 测量来证明。用 TNF-α 抑制剂治疗可改善肺部病变。我们得出结论，DBA/1 小鼠的 CIA 伴有肺炎症。虽然这两个疾病过程都受到内源性 IFN-γ 的控制，但缺乏严格的平行性表明它们的发病机制存在部分重叠。
