neuropeptide-y and Sjogren-s-Syndrome

A predominance of sensory neuropathy was earlier described in Sjögren's syndrome (SS), which might precede the presence of sicca symptoms. The mechanism of sensory neuropathy in SS is unknown. Therefore, the aim of this study was to determine the quantitative changes of the different neuropeptide containing nerve terminals and the immunocompetent cells in labial salivary glands of primary SS.. Immunohisto- and immunocytochemical methods were used for the detection of immunoreactive (IR) elements and the data were compared with the healthy controls.. All of the investigated IR nerve fibres were found in different quantity and localisation in both of control and SS glands. The density of them was changed variously in SS. The number of the substance P (SP), neuropeptide Y (NPY) (P < 0.05), galanin (GAL) IR nerve terminals was decreased, however, the number of vasoactive intestinal polypeptide (VIP) and tyrosine beta-hydroxylase (TH) IR nerve fibres (P < 0.05) was increased compared to the control. There were no IR immunocompetent cells in the control materials, however, a large number of them showed IR for SP (46.2%) and NPY (34.4%) in the SS. The IR was demonstrated mainly in the mast cells, plasma cells and some of the lymphocytes.. These neuropeptides might have a role in the sensory neuropathy; they might activate nociceptive and sympathetic pathways. Some neuropeptides (SP, NPY) are endogenous in the immune system and produced in certain conditions, e.g. inflammation and chronic autoimmune disorders such as SS, so they might participate in the neuroimmunomodulation and contribute to the atrophy, apoptosis and necrosis.

Topics: Adult; Aged; Female; Galanin; Humans; Lymphocytes; Male; Mast Cells; Microscopy, Electron; Middle Aged; Nerve Fibers; Neuroimmunomodulation; Neuropeptide Y; Neuroprotective Agents; Peripheral Nervous System Diseases; Plasma Cells; Salivary Glands, Minor; Sjogren's Syndrome; Substance P; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

A large number of nerve fibres containing different neuropeptides/transmitters are also found in the salivary glands. The number and the distribution of nerve fibres is altered in many diseases, including in Sjögren's syndrome.. Therefore in the present study the distribution and precise localisation of the nerve fibres containing the frequently observed neuropeptides were studied in the minor salivary glands.. Vasoactive intestinal polypeptide, neuropeptide Y, substance P, calcitonin gene-related peptide, somatostatin, nitric oxide synthase and tyrosine beta-hydroxylase antibodies were used as primary antisera, and then by the aid of avidin-biotin-peroxidase complex method the immunoreactive fibers in human labial glands (control and with Sjögren's syndrome) and in minor glands of the root of the rat's tongue were detected.. Large number of vasoactive intestinal polypeptide and nitric oxide synthase immunoreactive nerve fibres were seen around the acini. The neuropeptide Y and tyrosine beta-hydroxylase positive nerve fibres were mainly found around the blood vessels. Some of the IR fibers were also found around the excretory ducts. In the biopsy of patients with Sjögren's syndrome, the acini were destroyed and only few excretory ducts were seen. The number of the nerve fibres was significantly decreased and many degenerated fibres were also observed among the acini. The electron-microscopic examinations showed that the immunoreactive nerve fibres were in close association to the secretory cells, to the smooth muscle cells of blood vessels and to the immunocells. The synaptic gap between the nerve fibres and the target cells were 40-200 nm.. On the bases of the distribution of the different transmitters containing nerve fibres and their relationship to effector cells, the authors suppose that these transmitters control the function of the gland and regulate the blood flow. The close association to immunocells and decreasing the nerve fibres in Sjögren's syndrome imply that they may have also a role in the neuroimmunologic processes.

Topics: Adult; Autonomic Fibers, Postganglionic; Calcitonin Gene-Related Peptide; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; Male; Neuropeptide Y; Neurotransmitter Agents; Nitric Oxide Synthase; Salivary Glands, Minor; Sjogren's Syndrome; Substance P; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

Different neuropeptide-containing nerve fibers (vasoactive intestinal polypeptide, substance P, neuropeptide Y) and nitric oxide synthase (NOS) positive nerve fibers were investigated to clarify their role in the function of human labial glands using immunohisto- and immunocytochemical techniques. The distribution pattern of all immunoreactive nerve fibers was similar both in the control and in the Sjögren's syndrome specimens. A large number of thin varicose vasoactive intestinal polypeptide and NOS positive nerve fibers were seen around or in close contact with the acini. Some of the immunoreactive nerve fibers were associated with the salivary ducts and blood vessels. Substance P and neuropeptide Y immunoreactive nerve fibers were located mainly around the blood vessels. Immunocytochemistry demonstrated that some of the positive nerve fibers were in direct contact with the acini, blood vessels and with the lymphocytes. The gap between the membranes of immunoreactive nerve terminals and the target cells was 40 to 200 nm. The number of the nerve terminals in Sjögren's syndrome specimens was decreased and some degenerated axons were also found. These results suggest that these neuropeptides and nitric oxide might act as a neurotransmitter in the regulation of secretion and blood flow in the labial glands. These fibers might also alter the neuroimmunological processes, because the investigated neuropeptides are known to be immunoregulators.

Topics: Axons; Blood Vessels; Humans; Immunohistochemistry; Lip; Lymphocytes; Nerve Degeneration; Nerve Endings; Nerve Fibers; Neuropeptide Y; Neuropeptides; Nitric Oxide; Nitric Oxide Synthase; Regional Blood Flow; Salivary Ducts; Salivary Glands, Minor; Sjogren's Syndrome; Substance P; Vasoactive Intestinal Peptide; Vasodilator Agents

To assess the activity level of the autonomic nervous system in Sjögren's syndrome (SS) and to correlate this with stress.. Patients with SS (n = 12) and healthy controls (n = 10) were analysed for the content of vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) in their stimulated saliva by radioimmunoassays and for stress by the use of a modified Jenkins Activity Survey (JAS).. The data are expressed as median (interquartile range). Salivary VIP output (pg/min) and NPY output (pg/min) were high in SS compared with healthy controls (30.0 (15.6, 36.6) versus 12.3 (9.2, 24.0), p = 0.045, 4.8 (0.6, 24.1) versus 0.7 (0.0, 2.4), p = 0.038, respectively). Patients experienced only a little, but not significantly, more stress than the healthy controls (stress index -2.8 (-7.7, 6.9) versus -5.2 (-12.9, 2.7), p > 0.05). Stress in general was associated with high salivary VIP concentrations (r = 0.41, p = 0.05).. These findings show that adequately processed saliva (containing aprotinin and EDTA as neuropeptidase inhibitors) contains measurable amounts of marker peptides of the autonomic nervous system. Secondly, VIP concentration but not output may be affected by stress, which may act by decreasing watery salivary flow. In patients with SS, VIP and NPY outputs are increased. This may indicate increased leakage into saliva or efforts to compensate for the diminished salivary flow, or both.

Topics: Adult; Autonomic Nervous System; Female; Humans; Middle Aged; Neuropeptide Y; Radioimmunoassay; Saliva; Salivation; Sjogren's Syndrome; Stress, Psychological; Vasoactive Intestinal Peptide

The presence and spatial distribution of peptide-containing nerves in labial salivary glands from 10 Sjögren's syndrome patients were compared with those in salivary glands from 7 healthy controls.. Immunoperoxidase staining was used to demonstrate vasoactive intestinal peptide (VIP)-immunoreactive (IR) fibers, postganglionic sympathetic fibers containing the C-flanking peptide of neuropeptide Y (CPON), and sensory fibers containing calcitonin gene-related peptide (CGRP) and substance P.. Acini, intralobular ducts, small arteries, and postcapillary veins were richly innervated by VIP-IR fibers, whereas CPON-, CGRP-, and substance P-IR fibers were restricted to blood vessels. Peptide-containing nerves were found surrounding, but not in the middle of, the highly inflamed mononuclear cell areas.. This topologic distribution suggests involvement of VIP-IR fibers in vascular, motor, and secretory components of the reflex salivary secretion, whereas the distribution and the vasoactive actions of CPON, CGRP, and substance P suggest a role in the regulation of the salivary gland circulation, and thus of transcapillary flow. Excessive release may contribute to a neurogenic inflammation. Local depletion and absence of trophic neuropeptide stimuli may contribute to acinar atrophy.

Topics: C-Peptide; Calcitonin Gene-Related Peptide; Humans; Immunoenzyme Techniques; Neuropeptide Y; Neuropeptides; Peripheral Nerves; Reference Values; Salivary Glands; Sjogren's Syndrome; Substance P; Vasoactive Intestinal Peptide