Cytokine generation by T cells and monocytes was determined for 50 subjects aged 65 yr or older and concurrently studied young subjects individually matched to each old subject for sex, race, and national origin. Highly significant differences between cytokine levels of old and young subjects all were gender specific. For T cells stimulated with anti‐CD3 plus anti‐CD28 antibodies, mean ratios of IFN‐γ generation for healthy old to young subjects were 0.22 for men ( P <0.001; n =15) and 3.35 for women ( P <0.001; n =13), and those of IL‐17 were 0.30 for men ( P< 0.001) and no difference for women. CD8 T cells were the source of high IFN‐γ in healthy old women. For old men with an inflammatory or immune disease ( n =10), mean old to young ratios of T‐cell‐generated IFN‐γ and IL‐17 increased with disease severity up to 5.78 and 2.97 (both P <0.01), respectively, without changes for old women with similar diseases ( n =12). For differentiated LPS‐stimulated monocytes, old to young ratios of TNF‐α and IL‐6 generation were high only in women with immune or inflammatory disease (2.38, P <0.05 and 1.62, P <0.01, respectively), whereas ratios of IFN‐γ‐evoked IP‐10 chemokine were low in all groups. Alterations in immune cytokine profiles with aging show significant gender specificity.—Goetzl, E. J., Huang, M.‐C., Kon, J., Patel, K., Schwartz, J. B., Fast, K., Ferrucci, L., Madara, K., Taub, D. D., Longo, D. L. Gender specificity of altered human immune cytokine profiles in aging. FASEB J . 24, 3580–3589 (2010). www.fasebj.org
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