vasoactive-intestinal-peptide and Arthritis

Suitable biomarkers are essential for the design of therapeutic strategies in personalized medicine. Vasoactive intestinal peptide (VIP) has demonstrated immunomodulatory properties in autoimmune murine and ex vivo human models. Our aim was to study serum levels of VIP during the follow-up of an early arthritis (EA) cohort and to analyze its value as a biomarker predicting severity and therapeutic requirements.. Data from 91 patients on an EA register were analyzed (76% rheumatoid arthritis (RA), 24% undifferentiated arthritis, 73% women, and median age 54 years; median disease duration at entry, 5.4 months). We collected per protocol sociodemographic, clinical, and therapeutic data. VIP levels were determined by enzyme immunoassay in sera harvested from the 91 patients (353 visits; 3.9 visit/patient) and from 100 healthy controls. VIP values below the 25(th) percentile of those assessed in healthy population were considered low. To determine the effect of independent variables on VIP levels, we performed a longitudinal multivariate analysis nested by patient and visit. A multivariate ordered logistic regression was modeled to determine the effect of low VIP serum levels on disease activity at the end of follow-up.. VIP concentrations varied considerably across EA patients. Those fulfilling the criteria for RA had the lowest values in the whole sample, although no significant differences were observed compared with healthy donors. Disease activity, which was assessed using DAS28, inversely correlated with VIP levels. After a two-year follow-up, those patients with low baseline levels of VIP displayed higher disease activity and received more intensive treatment.. Patients who are unable to up-regulate VIP seem to have a worse clinical course despite receiving more intense treatment. Therefore, measurement of VIP levels may be suitable as a prognostic biomarker.

Topics: Adult; Aged; Arthritis; Arthritis, Rheumatoid; Biomarkers; Case-Control Studies; Female; Humans; Male; Middle Aged; Odds Ratio; Prognosis; Severity of Illness Index; Vasoactive Intestinal Peptide

The present study examined the peripheral effects of vasoactive intestinal peptide (VIP) on rat knee joint blood flow during acute and chronic inflammation. The involvement of joint nerves and synovial mast cells on these effects was also investigated. Prior to blood flow assessment, animals were deeply anaesthetised with ethyl carbamate (urethane; 2 mg kg(-1) i.p.). Local application of VIP (10(-13)-10(-9) mol) onto the capsular surface of normal rat knee joints caused a dose-dependent increase in synovial perfusion with an ED50 of 1.2 x 10(-11) mol. The dilator effect of the peptide was transient with the maximal response occurring approximately 1 min after drug administration. VIP-induced vasodilatation was blocked by co-administration of the VIP receptor antagonist VIP(6-28) (10(-9) mol). The inhibitory effect of the antagonist was consistent across the entire VIP dose range (P=0.01). The vasoresponsiveness to VIP was significantly attenuated in acutely inflamed joints; however, surgical denervation of acutely inflamed knees re-established the vasodilator effect of the neuropeptide. Topical application of VIP to 1- and 3-week adjuvant monoarthritic knees produced a hyperaemic response, which was not significantly different from normal (P=0.06 and 0.73 for 1- and 3-week adjuvant treated joints, respectively). Stabilisation of synovial mast cells by disodium cromoglycate (cromolyn) pretreatment did not alter the vasoresponsiveness to VIP in acute or chronically inflamed joints. The vasodilatatory effect of VIP is lost during acute knee joint inflammation and this abrogated effect is neurally dependent. In the chronic phase of knee joint inflammation, VIP-mediated hyperaemia recovers to normal levels. Synovial mast cells do not influence the vasomotor effects of exogenously applied VIP in inflamed knee joints.

Topics: Animals; Arthritis; Hindlimb; Joints; Male; Mast Cells; Rats; Rats, Wistar; Vasoactive Intestinal Peptide; Vasodilator Agents

Lower numbers of neuropeptide-containing fibers in arthritic joints have been found as compared to control joints. This may be the result of fiber depletion, necrosis of fibers, or proliferation of soft tissues without neural sprouting. To discriminate between these possibilities, we studied the relationships between soft tissue proliferation, changes in vascularity of synovial tissues, and changes in joint innervation during arthritis. Arthritis was induced in the knee joint of mice by a single subpatellar injection of methylated bovine serum albumin after previous immunization. Antibodies to protein gene product 9.5, S-100, and growth-associated protein-43 (GAP-43) were used to study the general innervation pattern. Antibodies to calcitonin gene-related peptide (CGRP), vasointestinal polypeptide (VIP), substance P (SP), and tyrosine hydroxylase (TH) were used to localize sensory (SP, CGRP, VIP) and sympathetic (TH) fibers. Blood vessels of the joint were studied with ink perfusion, GAP-43, and a vascular marker (LF1). Directly after the induction of arthritis, the synovial cavity was enlarged and filled with leukocytes. From day 4 onward, small sprouting blood vessels penetrated the avascular mass of cells in the joint cavity. After 1 week, the vascular sprouting activity and GAP-43 immunoreactivity were maximal, and after 2 weeks, vascular sprouting activity diminished. In the subsequent period, the synovia slowly regained their prearthritic appearance and thickness. The most pronounced changes in the general staining pattern of CGRP, SP, VIP, and TH were found in the periosteum. From 2 days to 4 weeks after the induction of arthritis, the layer of SP, CGRP, and VIP fibers in the femoral periosteum was thicker and more irregular. GAP-43 staining showed many terminal varicosities, which suggested sprouting of nerve fibers. From 2 days to 2 weeks after the induction of arthritis, the SP and CGRP fibers in the periosteum showed gradual depletion. In the thickened subsynovial tissues that were revascularized, no ingrowth of neural elements was found. As the total number of nerve fibers in the synovial tissue did not change, large parts of the synovia directly facing the joint cavity were not innervated at 1 week after the induction of arthritis. These results strongly suggest that periosteal SP and CGRP fibers were depleted during arthritis. Synovial proliferation without concomitant fiber growth is the main cause of the reduced number of immunocytochemica

Topics: Animals; Arthritis; Blood Vessels; Calcitonin Gene-Related Peptide; Knee Joint; Male; Mice; Mice, Inbred C57BL; Nerve Fibers; Nerve Tissue; Neuronal Plasticity; Reference Values; Serum Albumin, Bovine; Substance P; Synovial Membrane; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

The concentrations of immunoreactive vasoactive intestinal polypeptide (ir-VIP), immunoreactive pancreatic polypeptide (ir-PP), ir-somatostatin, and ir-secretin were measured in serum and synovial fluid from patients suffering from various inflammatory joint diseases. One group of patients were not taking any medication, while another group received anti-inflammatory treatment at the time of sampling. High levels of ir-VIP in the synovial fluid were observed in the untreated group of patients, and the concentration of ir-VIP in the synovial fluid was significantly higher than in parallel serum samples. On the other hand, no significant differences in the concentrations of the other peptides were observed either between serum and synovial fluid or between the two groups of patients. It is suggested that VIP is released locally at the inflammatory site and that VIP may be of significance in inflammatory disorders.

Topics: Adult; Aged; Arthritis; Female; Gastrointestinal Hormones; Humans; Male; Middle Aged; Pancreatic Polypeptide; Secretin; Somatostatin; Synovial Fluid; Vasoactive Intestinal Peptide

Substance P-, somatostatin-, vasoactive intestinal polypeptide- and cholecystokinin-like levels were measured in lumbar dorsal and ventral cord of polyarthritic rats and compared with those obtained in vehicle-treated rats taken as controls. Polyarthritis decreased substance P concentration in lumbar ventral cord and increased cholecystokinin level in lumbar dorsal cord, while the other two peptides did not show any change. The results are discussed in relation to immunohistochemical data found in the literature.

Topics: Animals; Arthritis; Arthritis, Experimental; Cholecystokinin; Peptides; Rats; Rats, Inbred Strains; Somatostatin; Spinal Cord; Substance P; Vasoactive Intestinal Peptide