neurokinin-a and Arthritis--Rheumatoid

Three types of tachykinin receptors, namely NK1, NK2 and NK3, are known to preferentially interact with substance P (SP), neurokinin A (NKA) and neurokinin B (NKB), respectively. We previously demonstrated that NK1 and NK2 receptors are present on human monocytes, SP and NKA inducing superoxide anion production and tumor necrosis factor-alpha (TNF-alpha) mRNA expression. NK2 receptor stimulation also triggered an enhanced respiratory burst in monocytes isolated from rheumatoid arthritis (RA) patients. This study was aimed to evaluate the in vitro and ex-vivo effects of cyclosporin A (CsA) on tachykinins-evoked TNF-alpha release from monocytes of healthy donors and RA patients. CsA (100 ng/ml) potently inhibited phorbol ester- and tachykinin-evoked TNF-alpha secretion. In RA patients treated with CsA (Sandimmun Neoral 2.5 mg/kg/day, a significant time-dependent reduction in TNF-alpha secretion from monocytes was measured. This may contribute to the CsA therapeutic activity in RA.

Topics: Arthritis, Rheumatoid; Carcinogens; Cells, Cultured; Cyclosporine; Humans; Immunosuppressive Agents; In Vitro Techniques; Monocytes; Neurokinin A; Peptide Fragments; Receptors, Neurokinin-1; Receptors, Neurokinin-2; Receptors, Neurokinin-3; Receptors, Tachykinin; Respiratory Burst; Substance P; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha

Topics: Aged; Arthritis, Rheumatoid; Cell Separation; Female; Humans; Male; Middle Aged; Monocytes; N-Formylmethionine Leucyl-Phenylalanine; Neurokinin A; Neurokinin B; Peptide Fragments; Receptors, Neurokinin-1; Receptors, Neurokinin-2; Receptors, Neurokinin-3; Substance P; Superoxides; Tetradecanoylphorbol Acetate

Three types of tachykinin receptors, namely NK1, NK2 and NK3, are known to preferentially interact with substance P (SP), neurokinin A (NKA) and neurokinin B (NKB), respectively. Experimental evidence indicates that SP and NKA modulate the activity of inflammatory and immune cells, including mononuclear ones. This study evaluated the effects of mammalian tachykinins and selective tachykinin agonists and antagonists on human monocytes isolated from healthy donors: SP, NKA and NKB all evoked a dose-dependent superoxide anion (O2-) production and the NK2 selective agonist [beta-Ala8]-NKA(4-10) induced a full response. The NK3 selective agonist senktide was inactive, while the NK1 selective agonists septide and [Sar9Met(O2)11]SP displayed some effects. These results indicate that NK2 and also some NK1 receptors are present in monocytes isolated from healthy donors. The role of tachykinin receptor activation in rheumatoid arthritis was also investigated, by measuring O2- production and TNF-alpha mRNA expression in monocytes isolated from rheumatoid patients. Tachykinins enhanced the expression of this cytokine in both control and rheumatoid monocytes and NK2 receptor stimulation was shown to trigger an enhanced respiratory burst in monocytes from rheumatoid patients. In conclusion, these results indicate that NK2 and NK1 receptors are present on human monocytes, the former being preferentially involved in rheumatoid arthritis.

Topics: Aged; Arthritis, Rheumatoid; Dose-Response Relationship, Drug; Female; Gene Expression; Humans; Male; Middle Aged; Monocytes; Neurokinin A; Neurokinin B; Receptors, Tachykinin; RNA, Messenger; Substance P; Superoxides; Tumor Necrosis Factor-alpha

Forty-one patients (37 female and four male) with signs and symptoms of temporomandibular joint arthritis, were separated into two diagnostic groups (group I: inflammatory; group II: degenerative/non-specific joint disease). They were examined clinically, fluid was aspirated from the joint with saline and venous blood samples were collected at the same time. The joint fluid and plasma samples were analysed for neuropeptide-like immunoreactivity, i.e. neuropeptide Y (NPY-LI), calcitonin gene-related peptide (CGRP-LI), substance P (SP-LI) and neurokinin A (NKA-LI), using competitive radioimmunoassays. The aim was to investigate any co-variation of the peptides in the joint fluid and plasma. In group I, the median values of peptide concentrations in joint fluid were SP-LI = 129, CGRP-LI = 75, NKA-LI = 36 and NPY-LI = 676 pmol/l and in group II, SP-LI = 52, CGRP-LI = 64, NKA-LI = 45 and NPY-LI = 318 pmol/l. There were no significant differences between the groups for peptide concentrations. In group I, all the neuropeptides were strongly correlated. In group II, SP-LI and NKA-LI were strongly correlated while CGRP-LI was weakly correlated with NPY-LI and NKA-LI. Multiple step-wise regression analysis showed that most of the variation in NPY-LI, CGRP-LI and SP-LI in group I was explained by NKA-LI, but the regression did not reach statistical significance in group II.

Topics: Adult; Aged; Arthritis; Arthritis, Psoriatic; Arthritis, Rheumatoid; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Neurokinin A; Neuropeptide Y; Osteoarthritis; Regression Analysis; Spondylitis, Ankylosing; Substance P; Synovial Fluid; Temporomandibular Joint Disorders

The contribution of the nervous system to the pathophysiology of rheumatoid arthritis has been proposed to be mediated by certain neuropeptides. Neuropeptide Y, calcitonin gene-related peptide, substance P, and neurokinin A are considered modulators of inflammatory joint disease. Parameters of pain, as well as occlusal signs of tissue destruction from the arthritic TMJ and the corresponding neuropeptide concentrations in TMJ synovial fluid, were investigated in patients with various inflammatory joint diseases. The patients with rheumatoid arthritis were also examined in a separate diagnostic group. Visual analog scale, palpatory tenderness, maximal voluntary mouth opening, and anterior open bite were correlated to neuropeptide-like immunoreactivities of the above four neuropeptides. It was found that high concentrations of calcitonin gene-related peptide and neuropeptide Y in TMJ fluid are associated with pain, impairment of mandibular mobility, and occlusal signs of TMJ destruction in patients with rheumatoid arthritis. The results indicated neuropeptide involvement in rheumatoid arthritis, proposing a potentiation of the symptoms and signs by the inflammatory action of calcitonin gene-related peptide and neuropeptide Y.

Topics: Adult; Arthritis; Arthritis, Rheumatoid; Calcitonin Gene-Related Peptide; Female; Humans; Inflammation Mediators; Male; Middle Aged; Neuroimmunomodulation; Neurokinin A; Neuropeptide Y; Neuropeptides; Pain; Pain Measurement; Range of Motion, Articular; Statistics, Nonparametric; Substance P; Synovial Fluid; Temporomandibular Joint Disorders

Arthroscopy was performed on 18 patients (19 joints) with temporomandibular joint arthropathy. Arthroscopic investigation revealed that 12 patients had disk derangement, including 3 patients with rheumatoid arthritis. Six patients had osteoarthrosis, including one patient with rheumatoid arthritis. Synovial fluid content of substance P-like immunoreactivity (SP-LI), neurokinin A (NKA-LI), calcitonin gene-related peptide (CGRP-LI), neuropeptide Y (NPY-LI) and vasoactive intestinal polypeptide (VIP-LI) were analysed using radioimmunoassay technique. All peptides analysed were found, although in various concentrations, in the different joints. There were no significant differences in concentrations of the peptides in the synovial fluid between patients in the various groups. No significant correlation was found between clinical symptoms and signs, arthroscopic findings, or use of analgesic/anti-inflammatory medication versus concentrations of peptides in the synovial fluid. In comparison with earlier findings in the knee joint significantly higher concentrations of SP-LI, CGRP-LI and NPY-LI were found in the TMJ.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Arthroscopy; Calcitonin Gene-Related Peptide; Cartilage, Articular; Female; Humans; Male; Middle Aged; Neurokinin A; Neuropeptide Y; Neuropeptides; Osteoarthritis; Substance P; Synovial Fluid; Synovitis; Temporomandibular Joint; Temporomandibular Joint Disorders; Vasoactive Intestinal Peptide

There is evidence that neuropeptides play a role in the development of arthritis. Synovial fluid from arthritic temporomandibular joints in patients with rheumatoid arthritis was therefore investigated for presence of the neuropeptides calcitonin gene-related peptide, substance P, neurokinin A and neuropeptide Y. All four peptides were found in the synovial fluid above plasma level, but calcitonin gene-related peptide showed the highest concentration and substance P the lowest.

Topics: Adult; Arthritis, Rheumatoid; Calcitonin Gene-Related Peptide; Female; Humans; Neurokinin A; Neuropeptide Y; Neuropeptides; Substance P; Synovial Fluid; Temporomandibular Joint Disorders

Topics: Arteriosclerosis; Arthritis, Rheumatoid; Autoimmune Diseases; Biological Products; Cytokines; Diabetes Mellitus; Disease; Eicosapentaenoic Acid; Glioma; Glycoproteins; Glycosylation; Humans; Immune Tolerance; Interleukin-1; Islets of Langerhans; Macrophages; Neurokinin A; Neurokinin B; Neuropeptides; Peptides; T-Lymphocytes; Transforming Growth Factors