Age-related changes in cytokine production by leukocytes in rhesus monkeys

Using a variety of experimental rodent and human models, age-related altera tions in cytokine production by immune cells have been described extensivel y. While the precise mechanism(s) responsible for such age-related changes in cytokine responses remain unclear, it seems likely that these changes ma y have a significant effect on immune cell function. In an attempt to clari fy such changes in aging primates, we examined cytokine production by white cells derived from a controlled colony of rhesus monkeys (Macaca mulatta). Non-fractionated whole blood and peripheral blood mononuclear cells (PBMCs ) were obtained from male monkeys of different ages (6-28 years), and were subsequently evaluated for their ability to express mRNA and protein for th e cytokines, IL-10, IL-6, IFN gamma, IL-1 beta, and TNF alpha, following in vitro stimulation with polyclonal mitogens. Our results suggest that white blood cells derived from aged rhesus monkeys exhibit a significant increas e in their ability to produce the Th2-associated cytokine, IL-10, upon stim ulation with lipopolysaccharide (LPS when compared to white cells derived f rom younger counterparts Similarly, a significant age-related decrease in t he expression of the Thlassociated cytokine, IFN gamma, was also observed u sing phytohemagglutinin (PHA)-stimulated PBMCs. No significant age-related differences in the production of IL-1 beta or TNF alpha were observed in re sponse to any stimulation, but there was limited evidence of an age-related increase in IL-6 production. Overall, our results suggest that a possible systemic change from a Th0/Th1 to a Th2-like cytokine profile occurs in cir culating leukocytes derived from aging primates. We believe that such age-r elated alterations in cytokine production may play a role in the reduced im mune responses observed in elderly human populations. (C) 2001, Editrice Ku rtis.