Circadian rhythmicity of interferon-gamma production in antigen-stimulated whole blood.

Recently, assessment of T cell function has been refined by the ability to measure cytokines produced by activated T cells. We developed a whole blood assay to detect antigen-activated T cells that produce IFN-gamma. With this assay we have found a large circadian variation in tetanus- (acrophase 00(00) p < 0.001) and PPD- (acrophase 00(08) p < 0.001) stimulated IFN-gamma production. IFN-gamma production is inversely correlated with plasma cortisol (r = -0.5), suggesting that variation in IFN-gamma production may be secondary to circadian variation in plasma cortisol levels (acrophase 11(06)). The demonstration of circadian rhythmicity in antigen-stimulated IFN-gamma production is relevant to the diagnostic use of whole blood assays and, in addition, may have implications for the therapy of immuno-inflammatory diseases.