Yoshino S, Yoshino J
Department of Microbiology, Saga Medical School, Japan.
Cell Immunol. 1998 May 1;185(2):153-7. doi: 10.1006/cimm.1998.1291.
We investigated a role for interleukin-4 (IL-4) in T-cell-mediated arthritis by employing a monoclonal antibody against IL-4 (11B11 mAb). As a model of T-cell-mediated arthritis, antigen-induced arthritis (AIA) in mice was used. To induce AIA, mice were immunized with methylated bovine serum albumin (mBSA) (day 0). On day 14, the animals were intraarticularly injected with mBSA into the ankle joint. 11B11 mAb was daily injected i.p. for a period of 10 days, commencing on the day of immunization with mBSA. We found that treatment with 11B11 mAb significantly enhanced the severity of AIA. The enhanced arthritis was also observed in mice injected i.v. with lymphoid cells from mBSA-immunized mice, followed by the intraarticular challenge injection of mBSA. The enhancement of AIA by the anti-IL-4 mAb was associated with a significant increase in the proliferative response of lymphoid cells to mBSA in mice treated with the mAb. The secretion of IL-4 as well as IL-5 decreased in 11B11 mAb-treated mice, while the production of IFN-gamma and IL-2 increased following mAb treatment. Thus, the neutralization of IL-4 by an anti-IL-4 mAb appeared to enhance AIA, suggesting a role for IL-4 in downregulating T-cell-mediated joint inflammation.
我们通过使用抗白细胞介素-4（IL-4）的单克隆抗体（11B11单克隆抗体）来研究IL-4在T细胞介导的关节炎中的作用。作为T细胞介导的关节炎模型，使用了小鼠抗原诱导性关节炎（AIA）。为诱导AIA，小鼠用甲基化牛血清白蛋白（mBSA）免疫（第0天）。在第14天，将动物踝关节内注射mBSA。从用mBSA免疫当天开始，每天腹腔注射11B11单克隆抗体，持续10天。我们发现用11B11单克隆抗体治疗显著增强了AIA的严重程度。在用mBSA免疫的小鼠静脉注射淋巴细胞，随后关节内注射mBSA的小鼠中也观察到了关节炎的加重。抗IL-4单克隆抗体对AIA的增强作用与用该单克隆抗体治疗的小鼠中淋巴细胞对mBSA的增殖反应显著增加有关。在11B11单克隆抗体治疗的小鼠中，IL-4以及IL-5的分泌减少，而在单克隆抗体治疗后，IFN-γ和IL-2的产生增加。因此，抗IL-4单克隆抗体对IL-4的中和作用似乎增强了AIA，提示IL-4在下调T细胞介导的关节炎症中起作用。
