Aging affects rat inflammatory peritoneal exudate composition and macrophage inflammatory mediator production in a strain-dependent manner

Abstract

The present study was designed to examine influence of aging on macrophage proinflammatory/anti-inflammatory capacity in rat model of thioglycollate-induced peritonitis. Peritoneal macrophages were isolated from young (3-months-old) and aged (18-months-old) Dark Agouti (DA) and Albino Oxford (AO) rats seven days post-injection of thioglycollate medium. Freshly isolated peritoneal exudate cells were examined for the expression of CD163, CCR7, CD14 and TLR4, whereas cytokine production (TNF-α, IL-6 and IL-10) and arginine metabolism end-products (NO and urea) were assayed in vitro under basal conditions and following stimulation with LPS. In DA rat inflammatory peritoneal exudate, aging diminished the frequency of cells with a “resolving macrophage” CD14+CD163+ phenotype. However, in AO rats, which exhibited stable frequency of CD14+CD163+ cells in inflammatory peritoneal exudate with aging, the proportion of CCR7-bearing peritoneal cells, presumably immigrating inflammatory monocytes, was diminished in aged animals. Under basal culture conditions, macrophages from aged rats of both strains released less amount of TNF-α, IL-6 and IL-10, but produced more urea than cells from young strain-matched rats. However, these changes were more pronounced in peritoneal macrophages from AO rats. Additionally, age-related decrease in the frequency of TLR4-expressing cells was observed among fresh peritoneal exudate cells from AO rats. Upon LPS stimulation, the production of prototypic inflammatory cytokines (TNF-α and IL-6) was diminished in macrophages from aged AO rats, whereas aging had the opposite effect on their production in DA rat macrophages. Moreover, aging increased NO production in LPS-stimulated macrophages from DA rats, whereas urea production was enhanced in macrophages from both strains, but this increase was strikingly more pronounced in macrophages from AO rats. Collectively, results suggest that aging affects inflammatory peritoneal exudate cellular composition and macrophage proinflamatory/immunomodulatory capacity in a strain- specific manner