interleukin-8 and Raynaud-Disease

To assess the serum profile of factors involved in endothelial, T-cell, and fibroblast interplay in patients with Raynaud's phenomenon (RP) associated with nailfold vodeocapillaroscopy (NVC) scleroderma findings and/or systemic sclerosis (SSc) marker autoantibodies, recently labeled as early SSc patients.. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), CCL2, CXCL8, IL-13, IL-33, and transforming growth factor-β (TGF-β) were measured in 24 early SSc patients, 48 definite SSc patients, and 24 osteoarthritis/fibromyalgia controls by multiplex suspension immunoassay. All SSc patients were investigated for the presence/absence of preclinical and clinical organ involvement, SSc marker autoantibodies, and NVC abnormalities.. Serum sICAM-1, CCL2, CXCL8, and IL-13 were increased in all SSc patients as compared to controls, and paralleled the severity of the disease subset (early SSc < limited cutaneous SSc < diffuse cutaneous SSc; p < 0.0001). Surprisingly, IL-33 was significantly higher in early SSc patients as compared to both controls (p < 0.01) and definite SSc patients (p < 0.05). In early SSc there were no differences in the investigated markers according to the functional and serological features assessed.. Our study suggests that an endothelial, T-cell and fibroblast activation can be present in patients with early SSc and it is associated with a distinct profile of circulating factors involved in the cross-talk of these cells. The marked increase of IL-33 in early SSc patients suggests new routes of investigation of cell-cell dynamics in target tissues predating overt disease manifestations, thus opening to new therapeutic approaches.

Topics: Adult; Animals; Antibodies, Antinuclear; Biomarkers; Capillaries; Cell Communication; Cells, Cultured; Chemokine CCL2; Disease Progression; Endothelial Cells; Female; Fibroblasts; Humans; Intercellular Adhesion Molecule-1; Interleukin-13; Interleukin-33; Interleukin-8; Interleukins; Male; Mice; Microscopic Angioscopy; Middle Aged; Raynaud Disease; Scleroderma, Systemic; T-Lymphocytes

Hand-arm vibration syndrome (HAVS) is a form of secondary Raynaud's phenomenon (RP) of occupational origin. In other forms of RP, blood and blood vessel wall interaction is one factor in the pathophysiology. Cytokines and cell adhesion molecules both play an important role in this interaction, and basal vascular tone and vasodilatation are regulated by nitric oxide.. Blood flow responses to acetylcholine (ACh) and sodium nitroprusside (SNP) and levels of soluble intercellular adhesion molecule-1 (sICAM-1) and the inflammatory cytokine interleukin 8 (IL-8) were measured in eight male patients with vibration white finger disease, which is part of HAVS, and in eight healthy matched male control subjects.. sICAM-1 levels were statistically higher (P = 0.02, Mann-Whitney U-test) and IL-8 levels (P < 0.01, Mann-Whitney) were significantly lower in the patient group. The patients with HAVS had significantly reduced vascular responses to SNP (P < 0.05, ANOVA).. In this study, we reveal differences in vascular responses to SNP that suggest there may be an impairment of the smooth muscle response to nitric oxide in patients with HAVS. The increase in sICAM-1 that occurs in patients with HAVS suggests that leucocyte adhesion is increased and that adherent neutrophils may contribute to the microvascular damage seen in this disease. The impeded flow of blood cells through the microcirculation may result in the low levels of circulating IL-8 due to the cytokine binding to erythrocytes. The possible role of NO activity in HAVS warrants further investigation.

Topics: Acetylcholine; Adult; Aged; Arm; Blood Flow Velocity; Endothelium, Vascular; Fingers; Hand; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Male; Middle Aged; Nitroprusside; Raynaud Disease; Reference Values; Vibration

Interleukin 8 (IL-8), a chemotactic cytokine produced by various cell types, displays structural homology to the connective tissue-activating peptide III. Little is known of the possible role of IL-8 in connective tissue disorders. We therefore determined serum concentrations of IL-8 and autoantibodies to IL-8 in 134 patients with systemic sclerosis (SSc) and related connective tissue disorders, as well as in pooled serum from 28 healthy control subjects by a sensitive enzyme-linked immunosorbent assay.. Interleukin 8 was undetectable in the pooled serum from 28 healthy controls, but detectable in serum samples from 24 of the 134 patients described above. It was detected in 13 of 60 patients with limited SSc and in eight of 48 patients with diffuse SSc. It was also detectable in one of three patients with eosinophilic fasciitis and in two of 10 patients with Raynaud's syndrome without skin involvement. In contrast, none of the three patients with morphea or the 10 patients with eosinophilia-myalgia syndrome had detectable IL-8 levels. We further determined the concentration of autoantibodies to IL-8 in the same serum samples. The values in healthy controls were 6.7 +/- 0.2 ng/mL (mean +/- SEM). Significantly elevated autoantibody levels were detected in patients with limited SSc (21.5 +/- 1.7), diffuse SSc (23.4 +/- 2.2), and Raynaud's syndrome (20.5 +/- 3.7). Elevated levels were also detected in patients with eosinophilic fasciitis (43.7 +/- 8.6) and morphea (14.7 +/- 3.2). Normal levels (7.5 +/- 2.0) were found in patients with eosinophilia-myalgia syndrome. Analysis of variance between the levels of autoantibodies to IL-8 and duration of the disease, extent of skin involvement, drug therapy, or serologic findings failed to show a significant correlation.. These results suggest that increased production of IL-8 may relate to activation of mononuclear phagocytes, fibroblasts, or endothelial cells, among other cell types, in patients with SSc, but not in those with eosinophilia-myalgia syndrome. This activation could be related to the production of autoantibodies to IL-8.

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Connective Tissue Diseases; Eosinophilia; Eosinophilia-Myalgia Syndrome; Fasciitis; Female; Humans; Interleukin-8; Male; Middle Aged; Raynaud Disease; Regression Analysis; Scleroderma, Localized; Scleroderma, Systemic