Experimental Lyme arthritis in the absence of interleukin-4 or gamma interferon

Experimental Lyme arthritis in the absence of interleukin-4 or gamma interferon
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DOI:
10.1128/iai.67.7.3329-3333.1999
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发表时间:
1999-07-01
影响因子:
3.1
通讯作者:
Reiner, SL
Reiner, SL
中科院分区:
医学2区
文献类型:
--
作者:
Brown, CR;Reiner, SL

文献摘要

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基因抵抗力和实验性莱姆关节炎的易感性分别与白细胞介素4(IL-4)或干扰素(干扰素-γ)的产生有关。为了确定疾病结局中对这些细胞因子的绝对需求,我们比较了野生型、IL-4缺乏、IL-4缺乏和干扰素-γ缺乏(干扰素-伽马度)小鼠的关节炎发生情况。在感染的第二周,易受感染的C3H型小鼠出现踝关节肿胀,而在C3H型干扰素-伽玛度小鼠,这种肿胀加剧。然而,它们在第21天的关节炎严重程度评分是相似的,C3H型和C3H型干扰素-伽玛度小鼠的关节炎消退也是相似的。在实验期间,抵抗关节炎的DBA小鼠没有出现脚踝肿胀。在测试的任何时间点,对照组DBA小鼠和DBA IL-4级小鼠的脚踝肿胀或关节炎严重程度评分没有差异。虽然21天时所有菌株的不同组织中螺旋体的存在是相似的,但在60天时,DBA IL-4度小鼠的血液、心脏和脾中的螺旋体出现率高于DBA、C3H和C3H干扰素-伽马度小鼠,DBA IL-4度小鼠产生疏螺旋体特异性抗体反应的能力也受到损害,特别是免疫球蛋白G1,因此,虽然干扰素-γ和IL-4对于关节炎易感性或耐药性并不是绝对必需的,但IL-4的产生似乎在产生疏螺旋体特异性抗体和清除螺旋体方面发挥了重要作用。
Genetic resistance and susceptibility to experimental Lyme arthritis have been linked with the production of interleukin-4 (IL-4) or gamma interferon (IFN-gamma), respectively. To determine the absolute requirement for these cytokines in disease outcome, we compared arthritis development in wild-type, IL-4-deficient IL-4 degrees, and IFN-gamma-deficient (IFN-gamma degrees) mice. While susceptible C3H mice developed swelling of ankle joints during the second week of infection, this swelling was exacerbated in C3H IFN-gamma degrees mice. Their arthritis severity scores at day 21, however, were similar, Resolution of arthritis was also similar between C3H and C3H IFN-gamma degrees mice. Arthritis-resistant DBA mice did not develop ankle swelling during the experimental period. There were no differences in ankle swelling or arthritis severity scores between control DBA mice and DBA IL-4 degrees mice at any of the time points tested. While the presence of spirochetes in various tissues was similar among all strains at day 21, DBA IL-4 degrees mice had a higher presence of spirochetes in blood, heart, and spleen than the DBA, C3H, and C3H IFN-gamma degrees mice did at day 60, DBA IL-4 degrees mice also had impaired ability to produce Borrelia-specific antibody responses, especially immunoglobulin G1, Thus, while IFN-gamma and IL-4 are not absolutely required for arthritis susceptibility or resistance, the production of IL-4 does appear to play an important role in Borrelia-specific antibody production and spirochete clearance.