Requirement of peptidergic sensory innervation for disease activity in murine models of immune hepatitis and protection by β-adrenergic stimulation

Renal Nerves Drive Interstitial Fibrogenesis in Obstructive Nephropathy

“…24 The autonomic nervous system has been implicated in acute and chronic inflammation of various organs. 25,26 Because CGRP has potent vasodilator activity, it has long been considered to be involved in aggravation of inflammation by increasing the blood flow, the number of circulating cells, and chemotactic factors. This possibility is supported by in vitro data demonstrating that exposure of endothelial cells to CGRP increases the expression of adhesion molecules for binding to neutrophils.…”

Neurokinin-1 Receptor Antagonists CP-96,345 and L-733,060 Protect Mice from Cytokine-Mediated Liver Injury

“…Although these nerve fibers are well known to affect peripheral inflammation in skin and joints as well as in gastrointestinal and respiratory tract (Holzer, 1988;Harrison and Geppetti, 2001), only limited information is available on their role in liver inflammation and fibrosis (Casini et al, 1990;Tiegs et al, 1999), and a hepatoprotective effect of NK-1R antagonists has never been demonstrated. The effects of SP and other tachykinins released from the peripheral endings of C-fibers are collectively referred to as "neurogenic inflammation", which has been characterized so far by flare, plasma extravasation, edema formation, and leukocyte infiltration (Holzer, 1988;Harrison and Geppetti, 2001;Severini et al, 2002).…”

“…These nerve fibers are detectable by SP and calcitonin gene-related peptide immunoreactivity in the portal tract of human (Stoyanova and Gulubova, 1998) and rodent (Markus et al, 1998;Tiegs et al, 1999) livers. Immunoreactive nerve fibers were capsaicin-sensitive, i.e., they were completely absent in adult mice that have been treated with capsaicin three days after birth to permanently deplete the C-fibers .…”

Activating Immunity in the Liver. I. Liver Dendritic Cells (but Not Hepatocytes) Are Potent Activators of IFN-γ Release by Liver NKT Cells

“…CD95-dependent hepatocyte apoptosis is associated with the parenchymal lesions (62,66). IL-6 (56, 67), phosphodiesterase inhibitors (68), or depletion of peptidergic sensory nerve fibers (69) can block or attenuate liver injury after Con A injection. Although Con A efficiently activates most CD3 ϩ T cells (including NKT cells), it is surprisingly inefficient in eliciting T cell-dependent liver injury in vivo: at least 10 4 -fold more Con A than ␣GalCer has to be injected to induce a comparable level of liver injury (500 g of Con A vs 50 ng of ␣GalCer/mouse).…”