title: The effects of nonsteroidal anti-inflammatory drugs on clinical outcomes, synovial fluid cytokine concentration and signal transduction pathways in knee osteoarthritis. A randomized open label trial.
abstract: OBJECTIVE
  We investigated the effects of celecoxib, diclofenac, and ibuprofen on the disease-specific quality of life, synovial fluid cytokines and signal transduction pathways in symptomatic knee osteoarthritis (OA).
  
  
  METHODS
  Ninety patients scheduled for a total knee arthroplasty (TKA) were randomized to six groups that were treated with low and high dosages of celecoxib, diclofenac or ibuprofen. At the time of the first admission (T0) and at surgery (T1 = 14 days after beginning of the nonsteroidal anti-inflammatory drugs (NSAIDs)), samples of knee synovial fluid were obtained from each patient for analysis. During the surgery the synovial tissue was harvested from the knee of patients. The Western Ontario and McMaster universities (WOMAC) score was used to evaluate the patient disease-specific quality of life at T0 and T1. Microarray tests performed at T0 and T1 were used to evaluate the effects of NSAIDs on Tumor necrosis factor (TNF)-alpha, Interleukin-6 (IL-6), IL8 and Vascular endothelial growth factor (VEGF) concentration in the synovial fluid. Western blot assays evaluated the effects of NSAIDs on MAP kinase (MAPK) signal transduction pathway in the synovial membrane.
  
  
  RESULTS
  NSAID treatment induced a statistically significant improvement in the WOMAC score and a statistically significant decrease in the IL-6, VEGF and TNF-alpha concentration in the synovial fluid. Higher dosages of NSAIDs provided a greater improvement in the disease-specific quality of life of patients and lower concentrations of pro-inflammatory cytokines in the synovial fluid. Inhibition of MAPKs was noted after NSAID treatment.
  
  
  CONCLUSIONS
  Short-term NSAID treatment improves the patient disease-specific quality of life with a parallel decrease in pro-inflammatory synovial fluid cytokine levels in knee OA. Signal transduction pathways may be involved in regulating the anti-inflammatory effects of NSAIDs. ClinicalTrial.gov: NCT01860833.
authors: Department of Health Science, School of Medicine, Magna Græcia University, Catanzaro, Italy.
authors: L
authors: L
authors: Gallelli
authors: O
authors: O
authors: Galasso
authors: D
authors: D
authors: Falcone
authors: S
authors: S
authors: Southworth
authors: M
authors: M
authors: Greco
authors: V
authors: V
authors: Ventura
authors: P
authors: P
authors: Romualdi
authors: A
authors: A
authors: Corigliano
authors: R
authors: R
authors: Terracciano
authors: R
authors: R
authors: Savino
authors: E
authors: E
authors: Gulletta
authors: G
authors: G
authors: Gasparini
authors: G
authors: G
authors: De Sarro
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D016207:Cytokines / Q000378:metabolism; D004008:Diclofenac / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000378:metabolism; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D011788:Quality of Life; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D013582:Synovial Fluid / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D011720:Pyrazoles; D013449:Sulfonamides; D004008:Diclofenac; D000068579:Celecoxib; D007052:Ibuprofen
keywords: Knee osteoarthritis; NSAID; Signal transduction pathways; Synovial fluid cytokines; WOMAC score