Calorie restriction modulates Th-1 and Th-2 cytokine-induced immunoglobulin secretion in young and old C57BL/6 cultured submandibular glands.

Abstract

Immunoglobulin production by the salivary gland plays an important role in oral and upper respiratory tract immunity. Age and/or disease may compromise salivary gland function. In order to gain insight into the role of calorie restriction (CR) on immunoglobulin (Ig) production, we determined the effect of ad libitum (AL) feeding and CR in young (3 months) and old (18-24 months) C57BL/6 mouse submandibular glands (SM). The SM tissues were fragmented and cultured in the absence (control) or presence of either Th-1 cytokines, such as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), or Th-2 cytokines, e.g. IL-4 and IL-5, for seven days. Culture supernatants were then analyzed for immunoglobulin A (IgA), IgM, and IgG2a levels by ELISA. Aging increased basal (control) IgA and IgM production by 3.1-and 3.7-fold, respectively, in AL mice. CR prevented the age-dependent rise of both IgA and IgM, maintaining levels equal to those of young AL mice. Interestingly, age resulted in a decrease of Th-1 cytokine-induced IgA and IgM, and increased IgG2a secretion in AL mice, while Th-2 cytokines did not appear to have an age effect. In general, CR suppressed Ig production induced by both Th-1 and Th-2 cytokines in young mice. In contrast, CR in old mice resulted in enhanced IgA and IgM production to levels similar to those in their young counterparts, while IgG2a was predominantly suppressed by Th-1 and not Th-2 cytokines. The data presented herein show, for the first time, the ability of CR to offset age-induced changes in submandibular gland Ig production, which may play a role in maintaining mucosal immune function, including proper oral health.