Diurnal rhythmicity of human cytokine production: A dynamic disequilibrium in T helper cell type 1/T helper cell type 2 balance?

Nikolai Petrovsky, Leonard C. Harrison

Research output: Contribution to journalArticlepeer-review

146 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5163-5168
Number of pages6
JournalJournal of Immunology
Volume158
Issue number11
Publication statusPublished - 1 Dec 1997
Externally publishedYes

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