title: Neuroimmune control of interleukin-6 secretion in the murine spleen. Differential beta-adrenergic effects of electrically released endogenous norepinephrine under various endotoxin conditions.
abstract: In a previous study we demonstrated a superfusion technique which allows for investigation of nerve-immune cell interaction in murine spleen. We demonstrated that under septic-like conditions in the presence of bacteria and lipopolysaccharide (LPS), electrically induced inhibition of interleukin 6 (IL-6) secretion was attenuated by the beta-adrenergic antagonist propranolol. This effect was now investigated more closely under various endotoxin conditions in order to dissect effects of bacteria and endotoxin: (A) bacteria-rich conditions (without penicillin/streptomycin [P/S] and without LPS), (B) LPS-enriched conditions (with P/S and with LPS), and (C) bacteria-free conditions (with P/S and without LPS). Under bacteria-rich conditions, norepinephrine (Emax = 10(-6) M, p = 0.012) and isoproterenol (Emax = 10(-6) M, p = 0.048) concentration-dependently inhibited IL-6 secretion from murine spleen slices in contrast to bacteria-free conditions. In a bacteria-free environment the beta-adrenergic antagonist propranolol did not attenuate the electrically induced inhibition of splenic IL-6 secretion. The insertion of bacterial filters in front of the superfusion chambers to avoid direct contact between bacteria and cells increased the electrically-induced inhibition of IL-6 secretion (p = 0.0036). Added LPS did not change the electrically-induced release of norepinephrine from presynaptic nerve terminals in murine spleen. The study demonstrates two different beta-adrenergic effects on IL-6 secretion of murine spleen slices under bacteria-rich or bacteria-free conditions.
authors.affiliation: Department of Internal Medicine I, University Medical Center Regensburg, Germany. rainer.straub@klinik.uni.regensburg.de
authors.forename: R H
authors.initials: RH
authors.lastname: Straub
authors.forename: M
authors.initials: M
authors.lastname: Herrmann
authors.forename: T
authors.initials: T
authors.lastname: Frauenholz
authors.forename: G
authors.initials: G
authors.lastname: Berkmiller
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: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001424:Bacterial Infections / Q000503:physiopathology; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009638:Norepinephrine / Q000502:physiology*; D010477:Perfusion; D013154:Spleen / Q000502:physiology*
chemical_list: D000319:Adrenergic beta-Antagonists; D004731:Endotoxins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D007545:Isoproterenol; D009638:Norepinephrine