interleukin-8 and Rheumatic-Diseases

Leukocyte infiltration during acute and chronic inflammation is regulated by exogenous and endogenous factors, including cytokines, chemokines and proteases. Stimulation of fibroblasts and human microvascular endothelial cells with the inflammatory cytokines interleukin-1beta (IL-1beta) or tumour necrosis factor alpha (TNF-alpha) combined with either interferon-alpha (IFN-alpha), IFN-beta or IFN-gamma resulted in a synergistic induction of the CXC chemokine CXCL10, but not of the neutrophil chemoattractant CXCL8. In contrast, simultaneous stimulation with different IFN types did not result in a synergistic CXCL10 protein induction. Purification of natural CXCL10 from the conditioned medium of fibroblasts led to the isolation of CD26/dipeptidyl peptidase IV-processed CXCL10 missing two NH2-terminal residues. In contrast to intact CXCL10, NH2-terminally truncated CXCL10(3-77) did not induce extracellular signal-regulated kinase 1/2 or Akt/protein kinase B phosphorylation in CXC chemokine receptor 3-transfected cells. Together with the expression of CXCL10, the expression of membrane-bound CD26/dipeptidyl peptidase IV was also upregulated in fibroblasts by IFN-gamma, by IFN-gamma plus IL-1beta or by IFN-gamma plus TNF-alpha. This provides a negative feedback for CXCL10-dependent chemotaxis of activated T cells and natural killer cells. Since TNF-alpha and IL-1beta are implicated in arthritis, synovial concentrations of CXCL8 and CXCL10 were compared in patients suffering from crystal arthritis, ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis. All three groups of autoimmune arthritis patients (ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis) had significantly increased synovial CXCL10 levels compared with crystal arthritis patients. In contrast, compared with crystal arthritis, only rheumatoid arthritis patients, and not ankylosing spondylitis or psoriatic arthritis patients, had significantly higher synovial CXCL8 concentrations. Synovial concentrations of the neutrophil chemoattractant CXCL8 may therefore be useful to discriminate between autoimmune arthritis types.

Topics: Autoimmune Diseases; Biomarkers; Cells, Cultured; Chemokine CXCL10; Chemokines, CXC; Cytokines; Dermis; Dipeptidyl Peptidase 4; Drug Combinations; Endothelial Cells; Fibroblasts; Humans; Infant, Newborn; Inflammation Mediators; Interleukin-8; Joint Diseases; Ligands; Peptide Fragments; Protein Isoforms; Receptors, Chemokine; Receptors, CXCR3; Rheumatic Diseases; Signal Transduction

Breast implants containing silicone have been used for approximately 30 years for breast augmentation or reconstruction. In general, the implants have been well tolerated and reports have indicated a high degree of patient satisfaction. Nonetheless, there have been anecdotal reports of patients with musculoskeletal complaints that have been attributed to silicone breast implants. To investigate this further, we prospectively examined 70 women with silicone breast implants who had complaints that they or their referring physicians thought were related to their implants. On clinical examination, the majority of the patients had fibromyalgia, osteoarthritis, or soft-tissue rheumatism. One patient had rheumatoid arthritis, which predated her implants, and one had Sjõgren's syndrome. Because many of our patients had myalgic symptoms, we further evaluated these patients by measuring circulating levels of soluble factors including interleukin-6, interleukin-8, tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1, and soluble interleukin-2 receptor, which have been previously found to be elevated in patients with inflammatory diseases. We found that the levels of these molecules in women with silicone breast implants were not different from those seen in normal subjects and were significantly less than those seen when examining chronic inflammatory disorders such as rheumatoid arthritis or systemic lupus erythematosus. In summary, our clinical and laboratory evaluation of symptomatic breast implant patients argues against an association of silicone breast implants with a distinctive rheumatic disease or a systemic inflammatory disorder. Given these findings and the clinical picture, it is our impression that most symptomatic women with silicone breast implants have well-delineated noninflammatory musculoskeletal syndromes. Moreover, these data fail to support the concept that their symptoms are due to a systemic inflammatory response related to their implants.

Topics: Breast Implants; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Middle Aged; Prospective Studies; Rheumatic Diseases; Silicones; Tumor Necrosis Factor-alpha

The content of interleukin-8 (IL-8) in the synovial fluid and its production by blood and synovial fluid mononuclear cells (PBMC and SFMC) was compared in rheumatoid arthritis (RA) and various other inflammatory rheumatic disorders. The study included 125 patients and 20 healthy individuals. The highest concentrations of IL-8 were found in the synovial fluids and culture supernatants of PBMC and SFMC from patients with seropositive RA. Only PBMC from seropositive patients, and not from other rheumatic diseases, exhibited significant spontaneous release of IL-8 that correlated with serum IgM rheumatoid factor titers. Gold sodium thiomalate (GST) and methotrexate (MTX) inhibited the spontaneous and stimulated IL-8 production by PBMC by 55-86% at 50 and 10 micrograms/ml, respectively. Two main conclusions were drawn: (1) rheumatoid factors appeared to be a major cause of enhanced IL-8 production in seropositive RA, and (2) inhibition of IL-8-mediated neutrophil migration and activation could be part of the mechanism of action of GST and MTX.

Topics: Anti-Inflammatory Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Gold Sodium Thiomalate; Humans; Immunoglobulin M; Interleukin-8; Methotrexate; Monocytes; Rheumatic Diseases; Rheumatoid Factor; Synovial Fluid