Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg, Gothenburg, Sweden.
J Infect Dis. 2012 Sep 1;206(5):687-96. doi: 10.1093/infdis/jis295. Epub 2012 Apr 16.
Staphylococcus aureus arthritis causes severe and rapid joint damage despite antibiotics. Thus, there is a need to identify new treatment targets in addition to antibiotics. Lately, interleukin 15 (IL-15) has been implicated both in osteoclastogenesis and in bacterial clearance-2 important issues in S. aureus-induced joint destruction. This has prompted us to investigate the importance of IL-15 in S. aureus-induced arthritis.
Toxic shock syndrome toxin-1 producing S. aureus was intravenously inoculated in IL-15 knockout and wildtype mice and in wildtype mice treated with anti-IL-15 antibodies (aIL-15ab) or isotype control antibody.
Absence of IL-15, either in knockout mice or after treatment with aIL-15ab, significantly reduced weight loss compared with controls during the infection. The severity of synovitis and joint destruction was significantly decreased in IL-15 knockout and aIL-15ab treated mice compared with controls. In IL-15 knockout mice there was a reduced number of osteoclasts in the joints. The host's ability to clear bacteria was not influenced in the IL-15 knockout mice, but significantly increased after treatment with aIL-15ab.
IL-15 is a mediator of joint destruction in S. aureus-induced arthritis and contributes to general morbidity, which makes this cytokine an interesting treatment target in addition to conventional antibiotics.
金黄色葡萄球菌关节炎尽管使用抗生素,仍会导致严重且迅速的关节损伤。因此,除了抗生素之外,还需要确定新的治疗靶点。最近,白细胞介素 15(IL-15)已被认为与破骨细胞生成和细菌清除有关-这是金黄色葡萄球菌引起的关节破坏的两个重要问题。这促使我们研究 IL-15 在金黄色葡萄球菌性关节炎中的重要性。
静脉内接种产毒性休克综合征毒素 1 的金黄色葡萄球菌于 IL-15 敲除和野生型小鼠中,并在野生型小鼠中用抗 IL-15 抗体(aIL-15ab)或同种型对照抗体治疗。
IL-15 缺失,无论是在敲除小鼠中还是在用 aIL-15ab 治疗后,与对照组相比,在感染过程中明显减轻了体重减轻。与对照组相比,IL-15 敲除和 aIL-15ab 治疗的小鼠的滑膜炎和关节破坏的严重程度明显降低。在 IL-15 敲除小鼠中,关节中的破骨细胞数量减少。IL-15 敲除小鼠的宿主清除细菌的能力不受影响,但在用 aIL-15ab 治疗后显著增加。
IL-15 是金黄色葡萄球菌性关节炎中关节破坏的介质,并导致一般发病率增加,这使得该细胞因子成为除常规抗生素以外的有吸引力的治疗靶点。