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, IFNgamma, IL-1beta, and TNFalpha, 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, IFNgamma, was also observed using phytohemagglutinin (PHA)-stimulated PBMCs. No significant age-related differences in the production of IL-1beta or TNFalpha 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.
Mascarucci
P
P
Laboratories of Neurosciences, Gerontology Research Center, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Taub
D
D
Saccani
S
S
Paloma
M A
MA
Dawson
H
H
Roth
G S
GS
Ingram
D K
DK
Lane
M A
MA
D000375:Aging / Q000276:immunology*; D000818:Animals; D016207:Cytokines / Q000235:genetics*; D015870:Gene Expression / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008934:Mitogens; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma