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 immun e system in vivo, we used two mouse models of T cell and TNF-alpha dependen t liver injury inducible by either concanavalin A or a combination of D-gal actosamine and staphylococcal enterotoxin B. Mice depleted of peptidergic s ensory 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 beta(2)-adrenergic agoni st salbutamol prevented, whereas chemical sympathectomy by 6-hydroxydopalni ne, deteriorated the disease. Hence. strategies reducing the activity of pe ptidergic sensory nerve fibres or stimulating beta(2)-adrenoreceptors, may be of benefit in immune-mediated liver disease. (C) 1999 Elsevier Science B .V. All rights reserved.