title: Endotoxin impedes vasoconstriction in the spleen: role of endogenous interleukin-1 and sympathetic innervation.
abstract: Processes relevant for an appropriate immune response such as immune cell traffic and recirculation require a tight control of blood supply to lymphoid organs. Interactions between endogenous cytokines and sympathetic nerve fibers in lymphoid organs can contribute to this control. The results reported in this paper show that 1) administration of low doses of lipopolysaccharide (LPS), an endotoxin derived from gram-negative bacteria, causes an increase in splenic blood flow (SBF); 2) this increase is mediated by the production of endogenous interleukin-1 (IL-1); 3) the effect of LPS on SBF requires an intact splenic sympathetic innervation; 4) the LPS-induced increase in SBF is exerted at the postganglionic level; 5) the endotoxin inhibits the vasoconstriction induced by the in vivo stimulation of the splenic nerve but does not affect the vasoconstriction induced by norepinephrine (NE); and 6) although IL-1 and LPS stimulate general sympathetic activity as reflected by increased peripheral vascular resistance, they do not increase NE concentration in splenic dialysates. Together these in vivo results indicate that endogenous IL-1 affects blood supply to the spleen by inhibiting the sympathetic vasoconstrictor tonus at a postganglionic, prejunctional level. This effect is expected to be relevant for immune cell recirculation, homing, and traffic as well as antigen trapping in the spleen, an organ specialized in the control of these processes during immune responses.
authors.affiliation: Institute of Physiology, Philipps-University Marburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Rogausch
authors.forename: A
authors.initials: A
authors.lastname: del Rey
authors.forename: A
authors.initials: A
authors.lastname: Kabiersch
authors.forename: W
authors.initials: W
authors.lastname: Reschke
authors.forename: J
authors.initials: J
authors.lastname: Ortel
authors.forename: H
authors.initials: H
authors.lastname: Besedovsky
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003714:Denervation; D003907:Dexamethasone / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D005730:Ganglionic Blockers / Q000494:pharmacology; D005938:Glucocorticoids; D007375:Interleukin-1 / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009411:Nerve Endings / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D013154:Spleen / Q000098:blood supply* / Q000294:innervation; D013564:Sympathetic Nervous System / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D004731:Endotoxins; D005730:Ganglionic Blockers; D005938:Glucocorticoids; D007375:Interleukin-1; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D014662:Vasoconstrictor Agents; D003907:Dexamethasone; D012110:Reserpine; D009638:Norepinephrine