Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi.
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.
Am J Physiol Renal Physiol. 2019 Nov 1;317(5):F1274-F1284. doi: 10.1152/ajprenal.00616.2018. Epub 2019 Mar 20.
Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder that is characterized by prevalent hypertension, renal injury, and cardiovascular disease. Numerous studies have reported a low prevalence and/or impaired function of regulatory T (T) cells in both patients with SLE and murine models of the disease. Evidence suggests that T cell dysfunction in SLE results from a deficiency in IL-2. Recent studies have reported that low-dose IL-2 therapy expands T cells in mouse models of SLE, but whether expanding T cells protects against hypertension and renal injury during SLE is unclear. To examine this question, female SLE (NZBWF1) and control (NZW) mice were injected with vehicle or recombinant mouse IL-2 three times in 24 h followed by single maintenance doses every 5 days for 4 wk. Treatment with IL-2 effectively expanded T cell populations in the peripheral blood, spleen, and kidneys. Circulating levels of anti-dsDNA IgG autoantibodies, a marker of SLE disease activity, were higher in SLE mice compared with control mice but were unaffected by IL-2 treatment. As previously reported by our laboratory, mean arterial pressure, measured in conscious mice by a carotid catheter, was higher in SLE mice than in control mice. Mean arterial pressure was significantly lower in IL-2-treated SLE mice compared with vehicle-treated SLE mice, suggesting that expanding T cells using low-dose IL-2 attenuates the development of hypertension. While the mechanism for the protection against hypertension is unclear, it does not appear to be related to the delay of SLE disease progression.
系统性红斑狼疮（SLE）是一种慢性多系统自身免疫性疾病，其特征是普遍存在高血压、肾损伤和心血管疾病。许多研究报告称，SLE 患者和疾病的小鼠模型中调节性 T（T）细胞的患病率低和/或功能受损。有证据表明，SLE 中的 T 细胞功能障碍是由于 IL-2 缺乏引起的。最近的研究报告称，低剂量 IL-2 疗法可在 SLE 的小鼠模型中扩增 T 细胞，但在 SLE 期间扩增 T 细胞是否能预防高血压和肾损伤尚不清楚。为了研究这个问题，我们用载体或重组鼠 IL-2 对雌性 SLE（NZBWF1）和对照（NZW）小鼠进行了 24 小时内三次注射，然后每隔 5 天给予单次维持剂量，共进行 4 周。IL-2 治疗有效地扩增了外周血、脾脏和肾脏中的 T 细胞群体。循环中抗 dsDNA IgG 自身抗体的水平，即 SLE 疾病活动的标志物，在 SLE 小鼠中高于对照小鼠，但不受 IL-2 治疗的影响。正如我们实验室之前报道的那样，通过颈动脉导管在清醒小鼠中测量的平均动脉压在 SLE 小鼠中高于对照小鼠。与载体治疗的 SLE 小鼠相比，IL-2 治疗的 SLE 小鼠的平均动脉压显著降低，这表明使用低剂量 IL-2 扩增 T 细胞可减轻高血压的发展。虽然保护高血压的机制尚不清楚，但它似乎与延缓 SLE 疾病进展无关。
