Anti-Inflammatory Role of Sympathetic Nerves in Chronic Intestinal Inflammation

Rainer H Straub ^1*, Florian Grum ¹, Ulrike G Strauch ¹, Silvia Capellino ¹, Frauke Bataille ², André Bleich ³, Werner Falk ¹, Jürgen Schölmerich ¹ and Florian Obermeier ¹

¹ Department of Internal Medicine I, University Hospital Regensburg, Germany
² Department of Pathology, University Hospital Regensburg, Germany
³ Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Germany

^* To whom correspondence should be addressed. E-mail: rainer.straub{at}klinik.uni-regensburg.de.

Accepted 25 February 2008

Abstract

Background: Substance P (SP) is a proinflammatory neuropeptide in colitis, whereas sympathetic neurotransmitters are antiinflammatory at high concentrations.

Aim and Methods: In all layers of the colon, nerve fibre densities of SP+ and sympathetic nerve fibres were investigated (22 Crohn's disease [CD], 6 diverticulitis, 22 controls). In addition, the nerve fibre repellent factor semaphorin 3C (SEMA3C) was studied. The functional role of the sympathetic nervous system was tested in dextran sodium sulphate (DSS) and Il10-/- colitis.

Results: In all layers, CD patients demonstrated a loss of sympathetic nerve fibres. Sprouting of SP+ nerve fibres was particularly observed in the mucosa and muscular layer in CD. SEMA3C was detected in epithelial cells, and there was a marked increase of SEMA3C - positive crypts in the mucosa of CD compared to controls. In CD, the number of SEMA3C - positive crypts were negatively related to the density of mucosal sympathetic nerve fibres. Sympathectomy reduced acute DSS colitis but increased chronic DSS colitis. Sympathectomy also increased chronic colitis in Il10-/- mice.

Conclusions: This study demonstrated a loss of sympathetic and an increase of SP+ nerve fibres in CD. SEMA3C, a sympathetic nerve repellent factor, is highly expressed in the epithelium of CD patients. In chronic experimental colitis, the sympathetic nervous system confers an antiinflammatory influence. Thus, the loss of sympathetic nerve fibres in the chronic phase of the disease is most probably a proinflammatory signal, which might be related to repulsion of these fibres by SEMA3C and other repellents.