EFFECTS OF CALORIE RESTRICTION ON TRANSFORMING GROWTH-FACTOR-BETA-1 AND PROINFLAMMATORY CYTOKINES IN MURINE SJOGRENS-SYNDROME

The present study was carried out to determine whether restricting die tary calories prevents salivary gland abnormalities and modulates expr ession of transforming growth factor beta and proinflammatory cytokine s, IL-6, and TNF alpha in major salivary glands (SG;) of autoimmune lu pus-prone (NZB x NZW)F-1 (B/W) female mice. These mice develop focal l ymphocytic interstitial and periductal round cell infiltrates in saliv ary glands similar to those of humans with Sjogren's syndrome, Weanlin g B/W mice were fed a nutritionally adequate semipurified diet either ad libitum (AL) or a calorie-restricted (CR; 40% less calories than AL ) diet. The mice were sacrificed at 3.5 months (young) and 8.5 months (old) of age, Histopathologic and histomorphometric analyses as well a s growth factor and cytokine protein and mRNA expression were carried out in the SG. Histomorphometric analysis of SG from young mice showed no differences between AL and CR mice, but old AL (vs old CR) had a 7 .3-fold higher focus score and a 34-fold increase in percentage area i nflammation. mRNA analysis revealed significantly higher levels of TGF beta 1 in SG of old CR (6.8-fold) mice. In contrast, CR reduced mRNA expression of proinflammatory cytokines (IL-6, 2.9-fold for young and 4.8-fold for old; TNF alpha, old 3.9-fold). By immunoblotting, signifi cantly higher levels of TGF beta 1 protein was detected in old CR mice (vs old AL; 13.2-fold). IL-6 and TNF alpha proteins were undetectable in both young and old CR groups, whereas an increase in IL-6 (4.7-fol d) and TNF alpha (9.3-fold) was observed in old AL mice. These results indicate that amelioration of the histological severity of disease in SG of B/W mice is paralleled and possibly mediated by increased expre ssion of immunosuppressive TGF beta 1 and decreased expression of proi nflammatory cytokines. (C) 1995 Academic Press, Inc.