Norepinephrine in mice inhibits secretion of splenic IL-6 during the dark period but stimulates its secretion in the light period-possible role of the corticosterone tone

In early morning hours, a rise of serum cytokines such as IL-6 was described. This study aimed to find reasons for this phenomenon focussing on NE and corticosterone. Mouse spleen slices were electrically stimulated (ES) in a microsuperfusion chamber in order to release endogenous NE. ES inhibited IL-6 secretion when animals were sacrificed at 03:00 and 06:00 (both p<0.001) but it increased its secretion from spleen slice removed at 09:00 (p=0.026). Prior administration of corticosterone or the glucocorticoid antagonist RU486 abrogated these ES effects. Endogenous NE via α- and β-adrenoceptors mediated this time-dependent differential effects. This study demonstrates that cooperation of endogenous NE and corticosterone are involved in a time-dependent fall or rise of splenic IL-6 secretion.