Richards H B, Satoh M, Shaw M, Libert C, Poli V, Reeves W H
Department of Medicine, Thurston Arthritis Research Center, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill 27599-7280, USA.
J Exp Med. 1998 Sep 7;188(5):985-90. doi: 10.1084/jem.188.5.985.
Pristane induces a lupus-like syndrome in nonautoimmune mice characterized by the development of glomerulonephritis and lupus-associated autoantibodies. This is accompanied by overproduction of interleukin (IL)-6, a cytokine linked with autoimmune phenomena. The goal of this study was to evaluate the role of IL-6 in autoantibody production in pristane-induced lupus. BALB/cAn IL-6-deficient (-/-) and -intact (+/+) mice were treated with pristane or phosphate-buffered saline, and autoantibody production was evaluated. Pristane induced high levels of immunoglobulin (Ig)G anti-single-stranded DNA, -double-stranded (ds)DNA, and -chromatin antibodies in IL-6(+/+), but not IL-6(-/-) mice by enzyme-linked immunosorbent assay. High titer IgG anti-dsDNA antibodies also were detected in sera from +/+, but not -/-, mice by Crithidia luciliae kinetoplast staining. The onset of IgG anti-dsDNA antibody production in +/+ mice occurred >5 mo after pristane treatment, well after the onset of nephritis, suggesting that these antibodies are not directly responsible for inducing renal disease. In contrast to anti-DNA, the frequencies of anti-nRNP/Sm and anti-Su antibodies were similar in pristane-treated IL-6(-/-) and IL-6(+/+) mice. However, levels were higher in the +/+ group. These results suggest that IgG anti-DNA and chromatin antibodies in pristane-treated mice are strictly IL-6 dependent, whereas induction of anti-nRNP/Sm and Su autoantibodies is IL-6 independent. The IL-6 dependence of anti-DNA, but not anti-nRNP/Sm, may have implications for understanding the patterns of autoantibody production in lupus. Anti-DNA antibodies are produced transiently, mainly during periods of disease activity, whereas anti-nRNP/Sm antibody levels are relatively insensitive to disease activity. This may reflect the differential IL-6 dependence of the two responses.
pristane可在非自身免疫小鼠中诱发狼疮样综合征，其特征为肾小球肾炎和狼疮相关自身抗体的产生。这伴随着白细胞介素（IL）-6的过度产生，IL-6是一种与自身免疫现象相关的细胞因子。本研究的目的是评估IL-6在pristane诱导的狼疮中自身抗体产生中的作用。用pristane或磷酸盐缓冲盐水处理BALB/cAn IL-6缺陷型（-/-）和野生型（+/+）小鼠，并评估自身抗体的产生。通过酶联免疫吸附测定法，pristane在IL-6（+/+）小鼠中诱导产生高水平的免疫球蛋白（Ig）G抗单链DNA、抗双链（ds）DNA和抗染色质抗体，但在IL-6（-/-）小鼠中未诱导产生。通过克氏锥虫动基体染色，在+/+小鼠血清中也检测到高滴度的IgG抗dsDNA抗体，但在-/-小鼠血清中未检测到。+/+小鼠中IgG抗dsDNA抗体产生的起始时间在pristane处理后>5个月，远在肾炎发作之后，这表明这些抗体并非直接导致肾脏疾病。与抗DNA抗体相反，在pristane处理的IL-6（-/-）和IL-6（+/+）小鼠中，抗nRNP/Sm和抗Su抗体的频率相似。然而，+/+组中的水平更高。这些结果表明，pristane处理的小鼠中IgG抗DNA和抗染色质抗体严格依赖IL-6，而抗nRNP/Sm和抗Su自身抗体的诱导则不依赖IL-6。抗DNA抗体而非抗nRNP/Sm抗体对IL-6的依赖性，可能对理解狼疮中自身抗体产生的模式具有重要意义。抗DNA抗体主要在疾病活动期短暂产生，而抗nRNP/Sm抗体水平对疾病活动相对不敏感。这可能反映了这两种反应对IL-6依赖性的差异。
