It is suggested that different neuropeptides regulate gastric mucosal integrity and participate in the development of chronic gastritis. The aim of this study was to examine the roles and changes of immunoreactive (IR) nerves and immunocompetent cells in human gastritis. Immunohistochemical, immunocytochemical, and confocal laser microscopic methods were used. All investigated nerve fibers were found in different quantities in the mucosa of both control and gastritis samples. The number of SP, NPY, and VIP IR nerve fibers increased significantly (P < 0.05) in gastritis. No IR immunocompetent cells (lymphocytes, plasma cells, mast cells) were found in the control, however, some showed NPY (16.8%) and SP (9.4%) immunoreactivity in chronic gastritis. The distance between nerve fibers and immunocompetent cells was 200 nm to 1 microm. In conclusion, the increased number of SP, NPY, and VIP IR nerves and IR immunocytes suggests that they participate in development of neurogenic inflammation, repairing processes of chronic gastritis.

Neuropeptides are able to modulate cytokine production by macrophages in response to various stimulators and have a major role in inflammation of different organs. Mammalian poly (ADP-ribose) polymerase (PARP) and nuclear factor kappa B (NF-jB) both have been suggested to play a crucial role in inflammatory disorders. Unregulated increase of tumor necrosis factor-a (TNF-a) may also be pathogenic in inflammatory diseases. The aim of this study was to investigate the correlation between the number of Substance P (SP) containing nerve fibers and activated immune cells using immunohisto-, immunocytochemical (EM) and confocal laser microscopic methods. To investigate expression and activation of immune cells gastric biopsy samples from patients with chronic gastritis were used. The number of SP containing nerve fibers and activated immune cells increased significantly in gastritis. Using monoclonal p65 antibody, activated NF-jB was found in inflamed mucosa but was absent in uninflamed mucosa. Immunobinding for the activated form of p65 of NF-jB was found in 22% of macrophages and 45% of lymphocytes. The number of immune cells showing IR for NF-jB, PARP and TNF-a correlated with the increasing number of SP containing fibres. Confocal laser microscopy was used to confirm the colocalization of SP in TNF-a and NFjB positive lymphocytes and mast cells in inflamed mucosa. Immunoelectronmicroscopic investigation confirmed that these cells belong to lymphocytes, mast cells and macrophages. Conclusions: The increase of SP in nerve fibers and in activated immune cells further activate the production of other proinflammatory mediators (e.g. TNF-a) and therefore generate the chronic inflammation.

Bidirectional interaction between immune and nervous systems is considered an important biological process in health and disease. However, little is known about the mechanisms involved in their interaction in the human liver. This study examines the distribution of intrahepatic NPY, SP immunoreactive (IR) nerve fibers and their antomical relationship with immunocells containing tumor necrosis factor-α (TNF-α) and nuclear factor κB (NF-κB) in patients with autoimmune hepatitis. Liver specimens were obtained from control liver and autoimmune hepatitis patients. The immunoreactivity was determined by immunohisto- and immunocytochemistry and confocal laser microscopy. In hepatitis, the number of NPY-IR and SP-IR nerve fibers increased significantly. These IR nerve fibers were in very close contact with the lymphocytes. In healthy controls, no NPY-IR, SP-IR or NF-κB IR lymphocytes and only a few TNF-α positive cells, were observed. In hepatitis, some of the lymphocytes showed immunoreactivity for SP and NPY in the portal area. Fluorescent double-labeled immunostaining revealed that in these cells NPY did not colocalize with TNF-α or NF-κB. However, some of the SP fluorescence-positive immune cells exhibited immunostaining for p65 of NF-κB, where their labeling was detected in the nuclei. Under the electronmicroscope, these cells could be identified (lymphocytes, plasmacells and mast cells). The gap between the IR nerve fibers and immunocells was 1 μm or even less. Overexpression of SP in lymphocytes may amplify local inflammation, while NPY may contribute to liver homeostasis in hepatitis. Neural immunomodulation (SP antagonists and NPY) might be a novel therapeutic concept in the management of liver inflammation.

SP release from nerve fibers, lymphocytes and mast cells together with TNF-α can enhance the development of gastric inflammation and participate in tissue damage in gastritis.

The intrahepatic distribution of nerve fibres is highly species dependent, therefore we searched for a species where the innervation pattern is similar to that of the human liver. Livers of rats, cats, guinea pigs and humans were used. The different nerve elements were identified by ABC immunohistochemistry and analysed semiquantitatively. Large numbers of neuropeptide Y (NPY) and dopamine-beta-hydroxylase immunoreactive (IR) nerve fibres were observed in the human and guinea pig liver, and they were in close contact with portal triads, central veins and ran parallel with liver sinuses. A few substance P, somatostatin and vasoactive intestinal polypeptide IR nerve fibres were also detected intralobularly, while galanin nerve fibres were only observed around portal triads. In the rat liver only a few NPY-positive nerve fibres were found, exclusively in portal tracts. Some nerve cell bodies (IR for NPY and somatostatin) were also found in the liver of guinea pigs, young cats and humans, therefore some of the nerve terminals might originate from these intrinsic ganglia. It can be concluded that the innervation pattern of the guinea pig liver shows the highest similarity to that of the human liver.