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

Using a variety of experimental rodent and human models, age- related alterations in cytokine production by immune cells have been described extensively. While the precise mechanism(s) responsible for such age- related changes in cytokine responses remain unclear, it seems likely that these changes may have a significant effect on immune cell function. In an attempt to clarify 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 the cytokines, IL- 10, IL- 6, IFN,IL- 1, and TNF, following in vitro stimulation with polyclonal mitogens. Our results suggest that white blood cells derived from aged rhesus monkeys exhibit a significant increase in their ability to produce the Th2- associated cytokine, IL- 10, upon stimulation with lipopolysaccharide (LPS) when compared to white cells derived from younger counterparts. Similarly, a significant age- related decrease in the expression of the Th1- associated cytokine, IFN, was also observed using phytohemagglutinin (PHA)- stimulated PBMCs. No significant age- related differences in the production of IL- 1 or TNF were observed in response 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 circulating leukocytes derived from aging primates. We believe that such age- related alterations in cytokine production may play a role in the reduced immune responses observed in elderly human populations.