interleukin-8 and Spondylitis--Ankylosing

The vagal nerve exerts an essential pathway in controlling the cholinergic anti-inflammatory reflex. Thus, the study is aimed at investigating the acute effect of a noninvasive transcutaneous vagus nerve stimulation on clinical disease activity and systemic levels of inflammation in patients with psoriatic arthritis or ankylosing spondylitis.. Twenty patients with psoriatic arthritis (PsA) and 20 patients with ankylosing spondylitis (AS) were included and stimulated bilaterally with a handheld vagal nerve stimulator for 120 seconds 3 times a day for 5 consecutive days. All patients were in remission. Cardiac vagal tone, clinical scores, CRP, and cytokine levels were assessed.. In PsA and AS, decreased heart rate was observed, confirming compliance. Furthermore, in PsA, a clear reduction of clinical disease activity associated with a 20% reduction in CRP was shown. In AS, a reduction in interferon-. This open-label study provides support for an anti-inflammatory effect of transcutaneous vagus nerve stimulation in patients with psoriatic arthritis and ankylosing spondylitis. The modulated immune response and reduced disease activity and CRP-levels raise the fascinating possibility of using neuromodulation as an add-on to existing pharmacological treatments.

Topics: Adult; Anti-Inflammatory Agents; Arthritis, Psoriatic; C-Reactive Protein; Cohort Studies; Cytokines; Female; Humans; Inflammation; Interleukin-10; Interleukin-8; Male; Middle Aged; Severity of Illness Index; Spondylitis, Ankylosing; Treatment Outcome; Vagus Nerve Stimulation

Dysbiosis has been recently demonstrated in patients with ankylosing spondylitis (AS) but its implications in the modulation of intestinal immune responses have never been studied. The aim of this study was to investigate the role of ileal bacteria in modulating local and systemic immune responses in AS.. Ileal biopsies were obtained from 50 HLA-B27. Adherent and invasive bacteria were observed in the gut of patients with AS with the bacterial scores significantly correlated with gut inflammation. Impairment of the gut vascular barrier (GVB) was also present in AS, accompanied by significant upregulation of zonulin, and associated with high serum levels of LPS, LPS-BP, iFABP and zonulin. In in vitro studies zonulin altered endothelial tight junctions while its epithelial release was modulated by isolated AS ileal bacteria. AS circulating monocytes displayed an anergic phenotype partially restored by ex vivo stimulation with LPS+sCD14 and their stimulation with recombinant zonulin induced a clear M2 phenotype. Antibiotics restored tight junction function in HLA-B27 TG rats.. Bacterial ileitis, increased zonulin expression and damaged intestinal mucosal barrier and GVB, characterises the gut of patients with AS and are associated with increased blood levels of zonulin, and bacterial products. Bacterial products and zonulin influence monocyte behaviour.

Topics: Acute Disease; Acute-Phase Proteins; Adherens Junctions; Animals; Anti-Bacterial Agents; Antigens, CD; Bacteria; Caco-2 Cells; Cadherins; Carrier Proteins; Case-Control Studies; Cholera Toxin; Chronic Disease; Dysbiosis; Endothelium; Fatty Acid-Binding Proteins; Gene Expression; Haptoglobins; HLA-B27 Antigen; Human Umbilical Vein Endothelial Cells; Humans; Ileitis; Ileum; Interleukin-8; Intestinal Mucosa; Junctional Adhesion Molecule A; Lipopolysaccharides; Membrane Glycoproteins; Membrane Proteins; Monocytes; Permeability; Protein Precursors; Rats; Rats, Transgenic; RNA, Messenger; Spondylitis, Ankylosing; Tight Junctions; Up-Regulation

Here we aimed to determine the therapeutic effect of allicin on ankylosing spondylitis (AS) and explore the mechanism(s) of action. AS mouse model was constructed by transferring the HLA-B2704 gene into Kunming mice and verified by RT-PCR and CT imaging. Verified AS mice were randomly divided into model group (n = 6) and allicin-treated groups (50, 100, and 200 mg/kg, resp., n = 6, p.o., for 2 months). Wild type mice were used as control (n = 6). The levels of AS-related inflammatory factors were measured by ELISA. mRNA and protein expressions of HLA-B27 were checked by RT-PCR and western blotting. As the results, the mouse model of AS was successfully established, and high-dose allicin could markedly alleviate spine inflammatory injury possibly via reducing the secretion of the inflammatory factors (IL-6, IL-8, and TNF- α ) sharply in AS mice. Moreover, allicin significantly inhibited HLA-B27 protein translation but failed to suppress HLA-B27 gene transcription in AS mice, indicating a posttranscriptional mechanism of this modulation. In conclusion, allicin has potential to be used for AS treatment as an anti-inflammatory nutraceutical.

Topics: Animals; Disease Models, Animal; Disulfides; Gene Expression Regulation, Neoplastic; HLA-B27 Antigen; Humans; Inflammation; Interleukin-6; Interleukin-8; Mice; Mice, Transgenic; Spondylitis, Ankylosing; Sulfinic Acids; Tumor Necrosis Factor-alpha

The objective of the study was to investigate the association between IL-8 and other biomarkers of endothelial dysfunction (MCP-1, V-CAM, I-CAM) and the disease activity scores in a sample of 54 patients with ankylosing spondylitis (AS) without use of biological agents. Fifty-four AS patients without treatment with anti-TNFs agents between 18 and 80 years old, who met modified New York criteria and at the same time the axial ASAS criteria, were evaluated using an epidemiological questionnaire that included among others clinical data, BASDAI, BASFI, ASQoL, ASDAS and plasma levels of CRP, ESR, MCP-1, IL-8, ICAM-1 and VCAM-1. IL-8 varied in proportion to disease activity rates (BASDAI and ASDAS) p < 0.05, being strongly correlated with the disease activity. The levels of adhesion molecules I-CAM and VCAM, as described in other studies, were positively correlated with predisposing factors for cardiovascular disease. IL-8 has shown to be strongly correlated with clinical markers of disease activity and inflammatory activity and may be an additional variable to the overall assessment of the activity of the AS.

Topics: Adult; Biomarkers; Cardiovascular Diseases; Chemokine CCL2; Endothelium, Vascular; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Male; Middle Aged; Predictive Value of Tests; Prognosis; Quality of Life; Risk Factors; Severity of Illness Index; Spondylitis, Ankylosing; Surveys and Questionnaires; Vascular Cell Adhesion Molecule-1

A role for NK cells in the regulation of autoimmunity has been demonstrated. Since there is a strong association between Ankylosing Spondylitis (AS) and HLA-B27, which is specifically recognized by the NK-inhibitory receptor KIR3DL1, this study evaluated the potential involvement of NK cells in AS. We studied 19 AS patients and 22 healthy volunteer donors and assessed the percentage, activity and receptor expression of peripheral blood NK cells. We also evaluated candidate-inflammatory mediators in sera. We found that AS patients have significantly higher percentages of NK cells. However, we found no differences between the ability of NK cells derived from AS and healthy controls to recognize target cells expressing HLA-B27. Remarkably, we observed that the NK-inhibitory receptor CEACAM1 (carcino-embryonic antigen-cell adhesion molecule) is highly expressed among AS-derived NK cells. Furthermore, engagement of CEACAM1 inhibited NK activity in these patients. Finally, we demonstrated that CEACAM1 expression is induced by IL-8 and SDF-1 (stromal cell derived factor), both of which are present in high levels in the sera of AS patients. These results may indicate that NK cells and CEACAM1 play a role in AS pathogenesis and implicate chemokines in the mechanism of CEACAM1 expression.

Topics: Adult; Antigens, CD; Autoimmunity; Cell Adhesion Molecules; Cells, Cultured; Gene Expression Regulation; HLA-B27 Antigen; Humans; Interleukin-8; Killer Cells, Natural; Male; Middle Aged; Receptors, Immunologic; Receptors, KIR; Receptors, KIR3DL1; Spondylitis, Ankylosing

Tetranectin (TN) was assessed in paired synovial fluid (SF) and serum (S) samples from 27 patients with rheumatoid arthritis (RA), 23 with seronegative spondylarthritis (SSA) and 22 with osteoarthritis (OA). RA patients had a stronger correlation between serum and SF TN and a higher SF/S TN ratio than did SSA and OA patients. Moreover, the SF/S TN ratio exceeded 1 in most RA patients but not in SSA and OA patients, indicating the possibility of intra-articular TN synthesis in RA. A strong correlation of serum and SF TN with known inflammatory markers was observed in RA. The TN/proteinase inhibitors (PIs: alpha1-antitrypsin, alpha2-macroglobulin) molar ratio in SF was lower in RA and SSA patients to a statistically significant degree than in OA patients. In RA, in contrast to SSA and OA, this ratio correlated positively with the SF interleukin-8 (IL-8), responsible for neutrophil recruitment and degranulation, and negatively with erythrocyte sedimentation rate, serum C-reactive protein and fibrinogen, known markers of disease activity. In conclusion, patients with RA showed lower serum TN levels, a higher SF/S TN ratio and a lower SF TN/PI molar ratio than did SSA and OA patients, suggesting the implication of TN in the impaired regulation of fibrinolysis associated with the inflammatory process.

Topics: Adult; Aged; alpha 1-Antitrypsin; alpha-Macroglobulins; Arthritis, Rheumatoid; Biomarkers; Blood Proteins; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Lectins; Lectins, C-Type; Male; Middle Aged; Osteoarthritis; Serologic Tests; Spondylitis, Ankylosing; Synovial Fluid