Tonic neurogenic inhibition of interleukin-6 secretion from murine spleen caused by opioidergic transmission

The peripheral nervous system and the immune system were shown to have neurohumoral interactions. This study extends observations that demonstrated neuronal modulation of spontaneous interleukin-6 (IL-6) secretion in the spleen by norepinephrine (NE) and beta-endorphin. Spontaneous IL-6 secretion in vivo was markedly reduced by removal of macrophages with the clodronate technique. Furthermore, spontaneous IL-6 secretion was significantly inhibited at physiological concentrations of cortisol (10(-7) M). In the presence of 10(-7) M, cortisol, addition of norepinephrine (NE; 10(-5) M) and isoproterenol (10(-6) and 10(-5) M) significantly increased spontaneous IL-6 secretion (+20%; P = 0.0280, P = 0.0005, and P = 0.0050, respectively). In contrast, addition of beta-endorphin significantly inhibited spontaneous IL-6 secretion in the presence of 10(-7) M cortisol (-40%; 10(-11) M, P = 0.0410; 10(-10) M, P = 0.0005). To study the effect of endogenously released transmitters on spontaneous IL-6 secretion, spleen dices were electrically stimulated with 1, 5, 10, 50, and 100 Hz. Spontaneous IL-6 secretion was markedly reduced at a frequency of 10 Hz with 10(-7) M cortisol present (P < 0.0001). This indicates that the combination of nerve firing at 5-10 Hz and physiological cortisol conditions inhibits spontaneous IL-6 secretion. Inhibition of spontaneous IL-6 secretion from spleen macrophages is most probably due to a net inhibitory effect of opioidergic transmission under these conditions.