title: Tonic neurogenic inhibition of interleukin-6 secretion from murine spleen caused by opioidergic transmission.
abstract: 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.
authors.affiliation: Department of Internal Medicine I, University Medical Center, Regensburg, Germany.
authors.forename: R H
authors.initials: RH
authors.lastname: Straub
authors.forename: M
authors.initials: M
authors.lastname: Dorner
authors.forename: J
authors.initials: J
authors.lastname: Riedel
authors.forename: M
authors.initials: M
authors.lastname: Kubitza
authors.forename: N
authors.initials: N
authors.lastname: Van Rooijen
authors.forename: B
authors.initials: B
authors.lastname: Lang
authors.forename: J
authors.initials: J
authors.lastname: Schölmerich
authors.forename: W
authors.initials: W
authors.lastname: Falk
mesh_terms: D000818:Animals; D004357:Drug Synergism; D004558:Electric Stimulation; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D009424:Nervous System Physiological Phenomena; D009638:Norepinephrine / Q000494:pharmacology; D013154:Spleen / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D001615:beta-Endorphin / Q000494:pharmacology / Q000502:physiology*; D000093242:Interleukin-6 Inhibitors
chemical_list: D006854:Hydrocortisone; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009638:Norepinephrine; D001615:beta-Endorphin; D000093242:Interleukin-6 Inhibitors