Adenoviral Delivery of Interleukin-10 Fails To Attenuate Experimental Lyme Disease
Adenoviral Delivery of Interleukin-10 Fails To Attenuate Experimental Lyme Disease
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DOI：
10.1128/iai.00808-08
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发表时间：
2008-12-01
影响因子：
3.1
通讯作者：
Mitchell, William J.
中科院分区：
文献类型：
--
作者：
Brown, Charles R.;Lai, Annie Y. -C.;Mitchell, William J.
C57 BL/6小鼠感染伯氏疏螺旋体后产生白细胞介素-10（IL-10）已被认为是维持对实验性莱姆病关节炎发展的抗性的机制。在目前的研究中，我们试图确定IL-10在关节炎和心脏炎易感C3 H小鼠感染过程中的作用。C3 H IL-10（-/-）小鼠感染导致关节肿胀和关节炎严重程度评分高于野生型C3 H小鼠。B的测量。关节或播散组织中的伯氏螺旋体数目表明在不存在IL-10的情况下更有效地清除螺旋体，类似于在C57 BL/6 IL-10（-/-）小鼠中报道的。然而，与先前的体外研究相反，C3 H IL-10（-/-）小鼠的感染导致感染关节中细胞因子KC、IL-1 β、IL-4和IL-12 p70的体内表达降低。最后，IL-10在C3 H小鼠感染关节中的腺病毒表达不能调节严重莱姆病关节炎的发展，并且对螺旋体清除或疏螺旋体特异性抗体产生没有影响。莱姆病的发展似乎与IL-10的调节无关。这些结果表明IL-10限制了感染B的关节炎抗性和敏感性小鼠品系中关节炎的发展。burgdorferi和增加的IL-10产生不能挽救该模型中病理学发展的遗传易感性。
Production of interleukin- 10 (IL-10) by C57BL/6 mice following infection with Borrelia burgdorferi has been proposed as a mechanism whereby resistance to the development of experimental Lyme arthritis is maintained. In the current study, we sought to determine the role of IL-10 during infection of arthritis- and carditis-susceptible C3H mice. Infection of C3H IL-10(-/-) mice led to increased joint swelling and arthritis severity scores over those of wild-type C3H mice. Measurement of B. burgdorferi numbers in joints or disseminated tissues indicated a more efficient clearance of spirochetes in the absence of IL-10, similar to that reported in C57BL/6 IL-10(-/-) mice. However, in contrast to previous in vitro work, infection of C3H IL-10(-/-) mice led to decreased in vivo expression of the cytokines KC, IL-1 beta, IL-4, and IL-12p70 in the infected joints. Finally, adenoviral expression of IL-10 in the infected joints of C3H mice was unable to modulate the development of severe Lyme arthritis and had no effect on spirochete clearance or Borrelia-specific antibody production. Development of Lyme carditis appeared to be independent of modulation by IL-10. These results suggest that IL-10 limits the development of joint inflammation in both arthritis- resistant and -susceptible mouse strains infected with B. burgdorferi and that increased IL-10 production cannot rescue genetic susceptibility to development of pathology in this model.