Sauder D N, Wong D, Laskin C
Department of Medicine, University of Toronto, Ontario, Canada.
J Invest Dermatol. 1993 Jan;100(1):42S-46S. doi: 10.1111/1523-1747.ep12355242.
Murine lupus and the analogous human disease systemic lupus erythematosus (SLE) in humans are characterized by multisystem disease accompanied by the production of numerous serum autoantibodies. The classic model of murine lupus is the New Zealand black mouse (NZB). In this strain anti-DNA antibodies are the most specific marker for the presence of murine lupus, in that this autoantibody parallels both the development and activity of the disease. Exposure to ultraviolet (UV) radiation is known to exacerbate the disease in both the murine and the human disease. UV irradiation of the skin increases serum levels of certain cytokines including interleukin-1 (IL-1), IL-6, and granulocyte/macrophage-colony stimulating factor (GM-CSF), which can influence B- and T-cell function. Recent studies have focused on the role of cytokines in SLE. We hypothesize that the ultraviolet (UV)-induced exacerbation in NZB mice in part is mediated by UV-induced cytokines such as IL-1. Eight-week-old female NZB and DBA/2 mice were exposed to UV irradiation. Sera and supernatants from spleen cell cultures were assayed for anti-DNA antibodies. After UV exposure, NZB mice showed a marked increase in such antibodies. Skin from both strains of mice was probed for IL-1 alpha mRNA before and after UV irradiation. At 24 h, DBA/2 mice had a slight increase in mRNA coding for IL-1 alpha, whereas a much greater increase in skin IL-1 alpha was seen in the NZB skin. This increase in IL-1 mRNA was associated with similar increases in IL-1 bioactivity. These data suggest that the mechanism underlying the UV-induced exacerbation of lupus is mediated in part by the cutaneous production of IL-1.
小鼠狼疮以及人类中与之类似的系统性红斑狼疮（SLE）的特征是多系统疾病，并伴有多种血清自身抗体的产生。小鼠狼疮的经典模型是新西兰黑鼠（NZB）。在该品系中，抗DNA抗体是小鼠狼疮存在的最特异性标志物，因为这种自身抗体与疾病的发展和活动都平行。已知暴露于紫外线（UV）辐射会使小鼠和人类疾病的病情加重。皮肤受到紫外线照射会增加某些细胞因子的血清水平，包括白细胞介素-1（IL-1）、IL-6和粒细胞/巨噬细胞集落刺激因子（GM-CSF），这些细胞因子会影响B细胞和T细胞功能。最近的研究集中在细胞因子在SLE中的作用。我们假设紫外线（UV）诱导的NZB小鼠病情加重部分是由紫外线诱导的细胞因子如IL-1介导的。将8周龄的雌性NZB和DBA/2小鼠暴露于紫外线照射下。检测脾细胞培养物的血清和上清液中的抗DNA抗体。紫外线照射后，NZB小鼠的此类抗体显著增加。在紫外线照射前后，检测两种品系小鼠皮肤中的IL-1α mRNA。在24小时时，DBA/2小鼠编码IL-1α的mRNA略有增加，而NZB小鼠皮肤中IL-1α的增加幅度要大得多。IL-1 mRNA的这种增加与IL-1生物活性的类似增加相关。这些数据表明，紫外线诱导狼疮病情加重的机制部分是由皮肤产生的IL-1介导的。
