Calorie restriction decreases proinflammatory cytokines and polymeric Ig receptor expression in the submandibular glands of autoimmune prone (NZB X NZW)F-1 mice

Calorie restriction or fish oil (enriched in n-3 fatty acids) supplementati on ameliorates glomerulonephritis and Sjogren's syndrome lesions in (NZB x NZW)F-1(B/W) mice. Enhanced proinflammatory cytokine expression and deposit ion of immune complexes are the important pathological events in the develo pment of Sjogren's syndrome. In the present study, we have examined the eff ect of calorie restriction and fish oil supplementation on the expression o f key inflammatory cytokines [gamma interferon (INF-gamma), interleukin-10 (IL-10), and IL-12] and polymeric immunoglobulin (Ig) receptor (pIgR) (rece ptor 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 calo rie restricted (CR) (40% less calories than AL) diet supplemented with 5% c orn 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 w as fragmented and cultured for 7 days and the culture supernatants assayed for IgA, IgM, and IgG2a levels by enzyme-linked immunosorbent assay. Result s revealed a significant increase in the expression of IFN-gamma, IL-10, an d 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. P IgR mRNA expression also remained unaltered in CR animals irrespective of a ge and dietary fat, while it was found significantly increased in AL fed mi ce. 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 diseas e 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.