Requirement of peptidergic sensory innervation for disease activity in murine models of immune hepatitis and protection by beta-adrenergic stimulation.
To investigate the interaction between the peripheral nervous and the immune system in vivo, we used two mouse models of T cell and TNF-alpha dependent liver injury inducible by either concanavalin A or a combination of D-galactosamine and staphylococcal enterotoxin B. Mice depleted of peptidergic sensory nerve fibres by capsaicin were protected from liver injury. Moreover, TNF-alpha production was significantly reduced. Examination of the effect of catecholamines on liver injury showed that the beta2-adrenergic agonist salbutamol prevented, whereas chemical sympathectomy by 6-hydroxydopamine, deteriorated the disease. Hence, strategies reducing the activity of peptidergic sensory nerve fibres or stimulating beta2-adrenoreceptors, may be of benefit in immune-mediated liver disease.
Tiegs
G
G
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Erlangen, Germany. gt@macpost.pharmakologie.uni-erlangen.de
Bang
R
R
Neuhuber
W L
WL
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002395:Catecholamines / Q000502:physiology; D006520:Hepatitis, Animal / Q000473:pathology / Q000503:physiopathology*; D007154:Immune System Diseases / Q000503:physiopathology*; D008099:Liver / Q000294:innervation / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009412:Nerve Fibers / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013563:Sympathectomy, Chemical
D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D000420:Albuterol; D002211:Capsaicin