Peritoneal exudate cells from long-lived rats exhibit increased IL-10/IL-1 beta expression ratio and preserved NO/urea ratio following LPS-stimulation in vitro

Abstract

In humans, usual aging, differently from successful aging, is associated with deregulation of proinflammatory/anti-inflammatory cytokine balance. The corresponding data from rat studies are limited. Therefore, we examined (i) cytokine messenger RNA (mRNA) profile of fresh peritoneal cells from 6-(adult), 24-(old), and 31-month-old (long-lived) AO rats and (ii) proinflammatory (IL-1 beta and IL-6) and antiinflammatory (IL-10) cytokine, NO, and urea production in their LPS-stimulated cultures. Comparing with adult rats, cells from old ones expressed lower amount of TNF-alpha and IL-6 mRNAs, but greater amount of IL-1 beta mRNA. On the other hand, cells fromlong-lived rats exhibited a dramatic increase in IL-10 mRNA expression followed by diminished TNF-alpha and IL-6 mRNA expression, and comparable expression of IL-1 beta mRNA relative to adult rats. Consequently, IL-10/IL-1 beta mRNA ratio was greater in cells from long-lived rats than in adult and old rats. In LPS-stimulated peritoneal cell cultures (contained = 95 % macrophages) from old rats, concentration of common proinflammatory cytokines was higher than in those from adult rats. Comparing with adult and old rats, in LPS-stimulated macrophage cultures from long-lived rats, TNF-alpha and IL-6 concentrations were lower; IL-1 beta concentration was comparable or greater (in respect to adult rats), whereas that of IL-10 was strikingly higher. Consistently, in macrophage cultures from long-lived rats, NO (iNOS activity marker)/urea (arginase activity marker) ratio was less and not different from that in old and adult rats, respectively. The study suggests that macrophages from longlived rats, differently from those of old ones, have substantial ability to limit proinflammatory mediator production, which may contribute to their longevity.