Wisconsin State Laboratory of Hygiene, University of Wisconsin-Madison, Madison, WI 53706, USA.
Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
Pathog Dis. 2017 Aug 31;75(6). doi: 10.1093/femspd/ftx073.
The role that cytokines play in the induction of Lyme arthritis is gradually being delineated. We showed previously that severe arthritis developed in a T-cell-driven murine model, even in mice lacking interleukin-17A (IL-17A) and administered anti-gamma-interferon (IFN-γ) antibody. Increased levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), two pro-inflammatory cytokines, were detected in cultures of popliteal lymph node cells obtained from these mice. We hypothesized that concomitantly administered anti-IL-6, anti-TNF-α and anti-IFN-γ antibodies would inhibit the development of arthritis in IL-17A-deficient mice. Our results showed that swelling of the hind paws and histopathological changes consistent with arthritis were significantly reduced in IL-17A-deficient mice that administered the three anti-cytokine antibodies. These results suggest that treatment with multiple anti-cytokine antibodies can abrogate the induction of Lyme arthritis in mice.
细胞因子在莱姆关节炎诱导中的作用正逐渐被描绘出来。我们之前曾表明,在 T 细胞驱动的小鼠模型中,即使在缺乏白细胞介素-17A(IL-17A)并给予抗γ干扰素(IFN-γ)抗体的小鼠中,也会发展出严重的关节炎。从这些小鼠的腘淋巴结细胞培养物中检测到两种促炎细胞因子,肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的水平升高。我们假设同时给予抗 IL-6、抗 TNF-α 和抗 IFN-γ 抗体将抑制 IL-17A 缺陷型小鼠关节炎的发展。我们的结果表明,接受三种抗细胞因子抗体治疗的 IL-17A 缺陷型小鼠的后爪肿胀和与关节炎一致的组织病理学变化明显减少。这些结果表明,用多种抗细胞因子抗体治疗可以消除莱姆关节炎在小鼠中的诱导。