Diurnal rhythmicity is a characteristic of neuroendocrine pathways but is less understood in relation to immune function. We asked whether cellular (type 1) or humoral (type 2) immune responses or type 1/type 2 balance exhibit diurnal rhythmicity in healthy humans, and, if so, whether this is related to plasma levels of Cortisol or melatonin, two hormones with immunomodulalory actions. LPS- or tetanus-stimulated human whole blood IFN-γ and IL-10 production, and the IFN-γ/IL10 ratio exhibited significant diurnal rhythmicity. The IFN-γ/IL-10 ratio peaked during the early morning and correlated negatively with plasma cortisol and positively with plasma melatonin. IFN-γ and, to a lesser extent, IL-10 production was sensitive to inhibition by exogenous cortisone; the IFN-γ/IL-10 ratio decreased by >70% after the administration of oral cortisone acetate (25 mg). Our findings support the concept that plasma cortisol and possibly melatonin regulate diurnal variation in the IFN-γ/IL-10 ratio. As IFN-γ and IL-10 have opposing effects on cellular immunity, changes in their balance would be anticipated to impose diurnal rhythmicity on cellular immunity. This implies that the nature of an immune response, e.g., to vaccination, may be modified by the time of day of Ag presentation and could be therapeutically manipulated by the administration of cortisol or melatonin.
|Number of pages||6|
|Journal||Journal of Immunology|
|Publication status||Published - 1 Dec 1997|