ABSTRACT

It is increasingly apparent that many important biological functions are subject to diurnal variation. Diurnal rhythms of immunological relevance include variation in the number of circulating T cells [1], the autologous mixed lymphocyte reaction [2], the phagocytic index [3] and urinary neopterin secretion [4]. Cytokines play a critical role in mediating and regulating immune effector function. Until recently little was known about diurnal

rhythmicity of cytokine production. If human cytokine production was subject to diurnal variation this might account for time-of-day related exacerbations in the symptoms of certain human immuno-inflammatory disorders, for example rheumatoid arthritis or asthma. The serum level of many cytokines is below the sensitivity threshold of available assays. Consequently, to address the question of whether human cytokine production is subject to diurnal variation, we applied a whole blood assay [5] to study diurnal changes in antigen or mitogen-stimulated whole blood cytokine production in healthy subjects [6,7]. The advantages of whole blood over purified peripheral blood mononuclear cells (PBMC) are that it can be assayed immediately and, being unmanipulated, most closely approximates the environment in vivo. In particular, whole blood contains physiological concentrations of hormones and other circulating factors that regulate T-cell function and could therefore contribute to diurnal variation in cytokine production.