Neuroimmunomodulation in the normal and inflamed human liver

Recent studies have demonstrated a pronounced influence by the autonomic nervous system on immune-mediated experimental hepatitis. These functions are most likely based on close anatomical relationships between nerve fibres and various immune cells in the liver. Therefore our aim was to investigate the precise localization and density of the nerve fibers and immune cell and their contacts in normal and inflamed human liver.

Methods: somatostatin (SOM), calcitonin gene-related peptide CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), galanin immunoreactive (IR) nerve elements and tumor necrosis factor alpha (TNF-α) and nuclear factor κB were detected (NF κB) by ABC immunohistochemistry.

Results: The quantitative analysis of the density of the different neuropeptide containing nerve fibres showed that the IR nerve fibres were found with different density. The number of SP IR nerve fibers and the TNF-α, NF κB immune cells (being lymphocytes, plasma cells, mast cells and Kupffer cells) increased significantly in hepatitis. 6.8% of the immunocytes were IR for SP and 4, 6% of them were IR for NPY. In several cases close contacts were detected between IR nerve fibres and the immune cells, where the gap between the nerve terminals and immune cells was less than 1µm.

Conclusions: The changes in the density of nerve fibres and immunocytes might be the consequences of the inflammation. The increased number of SP IR nerve fibres might play a crucial role in the regulation of liver functions. Modulation of autonomic nervous system functions may open novel therapeutic strategies in immune and inflammatory liver diseases.