Muthukumar A R, Jolly C A, Zaman K, Fernandes G
Department of Medicine, The University of Texas Health Science Center at San Antonio, 78229-3900, USA.
J Clin Immunol. 2000 Sep;20(5):354-61. doi: 10.1023/a:1006620130114.
Calorie restriction or fish oil (enriched in n-3 fatty acids) supplementation ameliorates glomerulonephritis and Sjögren's syndrome lesions in (NZB x NZW)F1(B/W) mice. Enhanced proinflammatory cytokine expression and deposition of immune complexes are the important pathological events in the development of Sjögren's syndrome. In the present study, we have examined the effect of calorie restriction and fish oil supplementation on the expression of key inflammatory cytokines [gamma interferon (INF-gamma), interleukin-10 (IL-10), and IL-12] and polymeric immunoglobulin (Ig) receptor (pIgR) (receptor for IgA and IgM) and the secretion of Ig in the submandibular glands (SMG) of B/W mice. Weanling B/W mice were fed either ad libitum (AL) or calorie restricted (CR) (40% less calories than AL) diet supplemented with 5% corn oil (CO) or 5% fish oil (FO) until 4 or 9 months of age. The SMGs were removed and a portion of the tissue used for semiquantitive determinations of IFN-gamma, IL-10, IL-12 (p40), and pIgR mRNA. The remaining SMG tissue was fragmented and cultured for 7 days and the culture supernatants assayed for IgA, IgM, and IgG2a levels by enzyme-linked immunosorbent assay. Results revealed a significant increase in the expression of IFN-gamma, IL-10, and IL-12 mRNA with age in AL fed mice, whereas CR fed mice maintained their levels to near those seen in young animals regardless of the dietary fat. PIgR mRNA expression also remained unaltered in CR animals irrespective of age and dietary fat, while it was found significantly increased in AL fed mice. CR significantly inhibited the elevated levels of IgA and IgG2a seen in aged mice. Interestingly, CR also influenced the Ig level in young animals. In summary, these results indicate that amelioration of autoimmune disease by CR in B/W mice is possibly mediated by the lowered mRNA expression of IFN-gamma, IL-10, IL-12, and pIgR and the reduced Ig secretion.
热量限制或补充富含n-3脂肪酸的鱼油可改善（新西兰黑鼠×新西兰白鼠）F1（B/W）小鼠的肾小球肾炎和干燥综合征病变。促炎细胞因子表达增强和免疫复合物沉积是干燥综合征发展过程中的重要病理事件。在本研究中，我们检测了热量限制和补充鱼油对B/W小鼠下颌下腺中关键炎性细胞因子[γ干扰素（IFN-γ）、白细胞介素-10（IL-10）和IL-12]及多聚免疫球蛋白（Ig）受体（pIgR）（IgA和IgM的受体）表达以及Ig分泌的影响。将断奶的B/W小鼠随意喂食（AL）或进行热量限制（CR）（比AL少40%的热量）饮食，并补充5%玉米油（CO）或5%鱼油（FO），直至4或9月龄。取出下颌下腺，一部分组织用于IFN-γ、IL-10、IL-12（p40）和pIgR mRNA的半定量测定。其余下颌下腺组织切碎并培养7天，通过酶联免疫吸附测定法检测培养上清液中IgA、IgM和IgG2a水平。结果显示，随意喂食的小鼠中，IFN-γ、IL-10和IL-12 mRNA的表达随年龄显著增加，而无论饮食脂肪如何，热量限制喂养的小鼠其水平维持在接近幼龄动物的水平。无论年龄和饮食脂肪如何，CR动物中的pIgR mRNA表达也保持不变，而在随意喂食的小鼠中发现其显著增加。CR显著抑制了老年小鼠中升高的IgA和IgG2a水平。有趣的是，CR也影响幼龄动物的Ig水平。总之，这些结果表明，B/W小鼠中CR对自身免疫性疾病的改善可能是通过降低IFN-γ、IL-10、IL-12和pIgR的mRNA表达以及减少Ig分泌来介导的。
