A bacteria‐induced switch of sympathetic effector mechanisms augments local inhibition of TNF‐α and IL‐6 secretion in the spleen

Abstract

It is believed that an inflammation-induced activation of the CNS leads to an inhibition of overshooting immune responses to prevent extensive local cytokine secretion. However, immunosuppression by the sympathetic nervous system may be unfavorable when bacteria are present locally and when TNF-α is necessary to overcome infection. We now report in a superfusion model, using mouse spleen slices, that although local Pseudomonas aeruginosa increased splenic TNF-α and IL-6 secretion severalfold over basal levels, electrically released neurotransmitters attenuated cytokine secretion to similar basal level as under bacteria-free conditions. Bacteria reversed noradrenergic inhibitory effector mechanisms: Under bacteria-free conditions, TNF-α secretion was very low and IL-6 secretion was mainly inhibited by α2-adrenoreceptor ligation. In the presence of bacteria, TNF-α and IL-6 secretion were high and IL-6 secretion was mainly inhibited by β-adrenoreceptor ligation. The α- to β-adrenoswitch of IL-6 inhibition in...