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

• Published in: The American journal of physiology Vol. 274; no. 4; p. R997
• Main Authors: Straub, R H, Dorner, M, Riedel, J, Kubitza, M, Van Rooijen, N, Lang, B, Schölmerich, J, Falk, W
• Format: Journal Article
• Language: English
• Published: United States 01-04-1998
• Subjects: Animals; beta-Endorphin - pharmacology; beta-Endorphin - physiology; Drug Synergism; Electric Stimulation; Female; Hydrocortisone - pharmacology; In Vitro Techniques; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - metabolism; Lipopolysaccharides - pharmacology; Macrophages - physiology; Mice; Mice, Inbred Strains; Nervous System Physiological Phenomena; Norepinephrine - pharmacology; Spleen - metabolism; Synaptic Transmission - physiology
• ISSN: 0002-9513
• DOI: 10.1152/ajpregu.1998.274.4.R997

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 slices 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.