interleukin-8 and Osteoarthritis--Hip

Compared with subcutaneous adipose tissue (SCAT), infrapatellar fat pad (IFP), the main knee intra-articular adipose tissue (IAAT), has an inflammatory phenotype in patients with osteoarthritis (OA). We phenotyped suprapatellar fat pad (SPFP) and hip acetabular fat pad (AFP), two other IAATs, to determinate the unique signature of IAATs compared with SCAT.. IFP, SPFP, AFP and autologous SCAT were obtained from patients with OA during total knee (n=38) or hip replacement (n=5). Fibrosis and adipocyte area were analysed by histology and vascularisation, leucocyte and mast cell infiltration were analysed by immunohistochemistry for von Willebrand factor, leucocytes and tryptase, respectively. Secretion of interleukin (IL)-6, IL-8 and prostaglandin E. Fibrosis, vascularisation and leucocyte and mast cell infiltration were greater in IAATs than SCAT, and levels of IL-6, IL-8 and PGE. IFP but also SPFP and AFP (gathered under the term 'IAAT') may play a deleterious role in OA by affecting joint homeostasis because of their inflammatory phenotype and their close interaction with synovium in the same functional unit.

Topics: Adipocytes; Adipose Tissue; Adolescent; Adult; Aged; CD36 Antigens; Culture Media, Conditioned; Dinoprostone; Fatty Acid-Binding Proteins; Female; Gene Expression; Hip Joint; Homeodomain Proteins; Humans; Interleukin-6; Interleukin-8; Knee Joint; Lipase; Lipoprotein Lipase; Male; Membrane Proteins; Middle Aged; Osteoarthritis, Hip; Osteoarthritis, Knee; Phenotype; PPAR gamma; RNA, Messenger; Subcutaneous Fat; Synoviocytes; Young Adult

Alpha-melanocyte-stimulating-hormone (α-MSH) has marked anti-inflammatory potential. Proinflammatory cytokines are critical mediators of the disturbed cartilage homeostasis in osteoarthritis, inhibiting anabolic activities and increasing catabolic activities in chondrocytes. Since human chondrocytes express α-MSH receptors, we evaluated the role of the peptide in modulating chondrocyte production of pro-inflammatory cytokines, matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in response to interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α).. Human articular chondrocytes were obtained from osteoarthritic joint cartilage from subjects undergoing hip routine arthroplasty procedures. The cells were cultured with or without α-MSH in the presence of IL-1β or TNF-α. Cell-free supernatants were collected and cells immediately lysed for RNA purification. Expression of cytokines, MMPs, TIMPs, iNOS was determined by Reverse Transcription Real-time Polymerase Chain Reaction and enzyme-linked immunosorbent assay. Griess reaction was used for NO quantification.. Gene expression and secretion of IL-6, IL-8, MMP-3, MMP-13 were significantly increased in IL-1β or TNF-α-stimulated chondrocytes; α-MSH did not modify the release of IL-6 or IL-8 while the peptide significantly reduced their gene expression on TNF-α-stimulated cells. A significant inhibition of MMP3 gene expression and secretion from IL-1β or TNFα-stimulated chondrocytes was induced by α-MSH. On the other hand, α-MSH did not modify the release of MMP-13 by cytokine-stimulated chondrocyte but significantly decreased gene expression of the molecule on TNF-α-stimulated cells. Detectable amount of TIMP-3 and TIMP-4 were present in the supernatants of resting chondrocytes and a significant increase of TIMP-3 gene expression and release was induced by α-MSH on unstimulated cells. TIMP-3 secretion and gene expression were significantly increased in IL-1β-stimulated chondrocytes and α-MSH down-regulated gene expression but not secretion of the molecule. TIMP-4 gene expression (but not secretion) was moderately induced in IL-1β-stimulated chondrocytes with a down-regulation exerted by α-MSH. IL-1β and TNF-α were potent stimuli for NO production and iNOS gene expression by chondrocytes; no inhibition was induced by α-MSH on cytokine-stimulated NO production, while the peptide significantly reduced gene expression of iNOS.. Our results underscore a potential anti-inflammatory and chondroprotective activity exerted by α-MSH, increasing TIMP-3 gene expression and release on resting cells and down- modulating TNF-α-induced activation of human chondrocytes. However, the discrepancy between the influences exerted by α-MSH on gene expression and protein release as well as the difference in the inhibitory pattern exerted by α-MSH in TNF-α- or IL-1β-stimulated cells leave some uncertainty on the role of the peptide on chondrocyte modulation.

Topics: alpha-MSH; Anti-Inflammatory Agents; Cells, Cultured; Chondrocytes; Gene Expression Regulation; Humans; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Interleukin-8; Matrix Metalloproteinases; Nitric Oxide; Nitric Oxide Synthase Type II; Osteoarthritis, Hip; Tissue Inhibitor of Metalloproteinases; Tumor Necrosis Factor-alpha

Synovial fibroblasts (SFs) contribute to the development of osteoarthritis (OA) by the secretion of a wide range of pro-inflammatory mediators, including cytokines and lipid mediators of inflammation. Previous studies suggest that electromagnetic fields (EMFs) may represent a potential therapeutic approach to limit cartilage degradation and control inflammation associated to OA, and that they may act through the adenosine pathway. Therefore, we investigated whether EMFs might modulate inflammatory activities of human SFs from OA patients (OASFs) treated with interleukin-1β (IL-1β), and the possible involvement of adenosine receptors (ARs) in mediating EMF effects. EMF exposure induced a selective increase in A(2A) and A(3) ARs. These increases were associated to changes in cAMP levels, indicating that ARs were functionally active also in EMF-exposed cells. Functional data obtained in the presence of selective A(2A) and A(3) adenosine agonists and antagonists showed that EMFs inhibit the release of prostaglandin E(2) (PGE(2)) and the proinflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8), while stimulating the release of interleukin-10 (IL-10), an antinflammatory cytokine. These effects seem to be mediated by the EMF-induced upregulation of A(2A) and A(3) ARs. No effects of EMFs or ARs have been observed on matrix degrading enzyme production. In conclusion, this study shows that EMFs display anti-inflammatory effects in human OASFs, and that these EMF-induced effects are in part mediated by the adenosine pathway, specifically by the A(2A) and A(3) AR activation. Taken together, these results open new clinical perspectives to the control of inflammation associated to joint diseases.

Topics: ADAM Proteins; Adult; Aged; Aged, 80 and over; Cells, Cultured; Cyclic AMP; Cytokines; Dinoprostone; Dose-Response Relationship, Drug; Electromagnetic Fields; Female; Fibroblasts; Humans; Inflammation Mediators; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Matrix Metalloproteinases; Middle Aged; Osteoarthritis, Hip; Purinergic P1 Receptor Agonists; Purinergic P1 Receptor Antagonists; Receptor, Adenosine A2A; Receptor, Adenosine A3; Receptors, Purinergic P1; RNA, Messenger; Synovial Membrane

To determine by genetic association analysis whether the 4q functional candidate genes IGFBP7, ADAMTS3, and IL8 might encode for susceptibility to osteoarthritis (OA).. Expression of IGFBP7, ADAMTS3, and IL8 in adult OA articular cartilage chondrocytes was demonstrated by reverse transcription-polymerase chain reaction. The genes were screened for common polymorphic DNA variants by direct sequencing of exons, intron-exon boundaries, and the 5' and 3' untranslated regions. The variants were genotyped in the female probands from the 146 families which each contained two or more sisters who had undergone total hip replacement (THR) and in 375 female controls matched for age. Variants showing evidence for association were subsequently genotyped in 244 female-THR patients with OA. Allele frequencies between the probands (or patients) and the controls were compared by chi(2) analysis.. Fourteen common variants were identified in the three genes. An ADAMTS3 single nucleotide polymorphism was associated in the probands (p = 0.015) and an ADAMTS3 insertion/deletion approached significance (p = 0.059). However, neither variant was associated in the additional 244 patients with hip OA, with p values of 0.12 and 0.19, respectively.. The analysis implies that the chromosome 4q female hip OA susceptibility is not coded for by polymorphism within the functional candidates IGFBP7, ADAMTS3, or IL8.

Topics: ADAM Proteins; ADAMTS Proteins; Aged; Cartilage, Articular; Chondrocytes; Chromosomes, Human, Pair 4; Endopeptidases; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Insulin-Like Growth Factor Binding Proteins; Interleukin-8; Middle Aged; Osteoarthritis, Hip; Procollagen N-Endopeptidase

The aim of this prospective study was to determine the local concentrations of inflammatory mediators in various tissue types frequently affected by trauma to estimate the role of prestored cytokine release by mechanical tissue trauma in the induction of a systemic inflammatory response syndrome. The degree of tissue damage, evaluated by its systemic release of inflammatory mediators, represents an important factor concerning the outcome of trauma patients. Clinical trials indicate that the kind of traumatized tissue influences the cytokine pattern measured in patients blood afterwards. However, the tissue-specific mediator composition underlying this systemic mediator release is rarely elucidated. Upon approval of the local IRB/EC, skin, subcutaneous fat, muscle, cancellous bone, and lung tissue were obtained during standard surgical procedures. The protein-based concentrations of Interleukin (IL)-6, IL-8, IL-10, and IL-12 were determined in tissue homogenates by enzyme-linked immunoabsorbant assay (ELISA; n = 60 samples). Albumin was measured to evaluate the degree of blood contamination of tissue samples. IL-6 and IL-8 were consistently detectable in more than 95% of the tissue specimens. Lung and cancellous bone presented by far the highest concentrations of these cytokines, whereas skin, subcutaneous fat, and muscle showed significantly lower levels. IL-10 was not detectable in 88%; IL-12 could not be measured in 63% of the samples. Cytokine concentrations did not correlate with the amount of albumin measured in tissue specimens. Due to their consistent presence at the tissue level, high systemic concentrations of IL-6 and IL-8 in patients blood, seen after pulmonary trauma, long bone fractures, or soft tissue injury, may be interpreted as an overspill of local trauma mediators. This indicates their relevance in post-traumatic monitoring. Furthermore, albumin is a suitable and necessary indicator to evaluate influences of possible blood contamination in tissue samples.

Topics: Adipose Tissue; Aged; Aged, 80 and over; Albumins; Bone and Bones; Cytokines; Femoral Neck Fractures; Humans; Inflammation Mediators; Interleukin-10; Interleukin-12; Interleukin-6; Interleukin-8; Intraoperative Period; Lung; Lung Neoplasms; Middle Aged; Muscle, Skeletal; Organ Specificity; Osteoarthritis, Hip; Prospective Studies; Proteins; Skin; Systemic Inflammatory Response Syndrome; Wounds, Nonpenetrating

Bone turnover markers (osteocalcin, bone-ALP, beta-crosslaps--CTX) and cytokines (IL-1 alpha, IL-8 and IL-10) in hip joint fluid were analyzed in patients with aseptic loosening of prosthesis before revision surgery, in patients with rheumatoid arthritis and with idiopathic coxarthrosis for comparison.. Bone turnover markers were determined by electrochemiluminescence, colorimetric or ELISA method and cytokines by ELISA in joint fluid collected at the beginning of the surgery.. Patients with loose implants had lower concentration of the resorption marker than cases with rheumatoid arthritis and coxarthrosis (7771 +/- 3322 vs 25986 +/- 16059 p < 0.01 and 23047 +/- 32556 pmol/L, p < 0.003) and over tenfold lower concentration of osteocalcin, the bone formation marker (p < 0.04 i p < 0.01). Concentration of IL-8 was elevated and similar in patients with loosening and rheumatoid arthritis while in cases with osteoarthrosis the mean value was twice lower. The anti-inflammatory IL-10 was highly elevated only in cases with prosthesis loosening. Additionally, a negative correlation was observed between CTX and IL-10 was and positive between IL-10 and time to revision surgery.. We conclude that increased local production of inflammatory cytokines leading to uncoupling of bone turnover is a part of the loosening process.

Topics: Aged; Aged, 80 and over; Alkaline Phosphatase; Arthritis, Rheumatoid; Arthroplasty, Replacement, Hip; Biomarkers; Bone Resorption; Collagen; Colorimetry; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Hip Joint; Humans; Interleukin-1; Interleukin-10; Interleukin-8; Male; Middle Aged; Osteoarthritis, Hip; Osteocalcin; Peptide Fragments; Prosthesis Failure; Synovial Fluid

Concentrations of prostaglandin E2, interleukin-6, and interleukin-8 were determined in the hip joint synovial fluid of 20 patients undergoing primary (n = 12) and revision (n = 8) total hip arthroplasties. Levels of soluble adhesion molecules were also investigated in these patients. There was a significant and marked increase in levels of prostaglandin E2 (P < .001), interleukin-6 (P < .011), interleukin-8 (P < .0002), soluble intercellular adhesion molecule 1 (P < .07), soluble vascular adhesion molecule 1 (P < .0006), and soluble endothelial leukocyte adhesion molecule 1 (P < .0003) in joint fluid of patients undergoing revision. On the basis of these observations, it is suggested that synovial fluid and its inflammatory contents could play a significant role in the pathogenesis of aseptic loosening in total hip arthroplasties.

Topics: Aged; Aged, 80 and over; Cell Adhesion Molecules; Dinoprostone; Female; Hip Prosthesis; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Middle Aged; Osteoarthritis, Hip; Postoperative Complications; Prosthesis Failure; Reference Values; Reoperation; Synovial Fluid