title: Clinical significance of IL-18, IL-15, IL-12 and TNF-alpha measurement in rheumatoid arthritis.
abstract: The aim of the study was to evaluate the clinical significance of serum (S) and synovial fluid (SF) interleukin (IL)-18, IL-15, IL-12 and the tumor necrosis factor alpha (TNF-alpha) measurements in relation to laboratory and clinical measures of disease activity of patients with active rheumatoid arthritis (RA). Sixty-four patients with RA and 25 patients with osteoarthritis (OA) were included in this study. RA activity was determined using the Disease Activity Score (DAS) 28 index. Concentrations of IL-18, IL-15, IL-12 and TNF-alpha were measured by ELISA. Serum C-reactive protein (CRP) levels were also determined. Cross-sectional correlations between S and SF levels of cytokines and values of DAS 28 index were calculated. The results have shown that IL-18, IL-15, IL-12 and TNF-alpha levels in S and SF of patients with RA were significantly higher than the levels obtain from patients with OA (p<0.01). Significantly higher levels of IL-18, IL-15 and TNF-alpha were found in the SF compared to the S of patients with RA (p<0.01). Significantly higher S and SF levels of all four cytokines and serum CRP values were found in RA patients with high disease activity (DAS 28>5.1) compared to those with mild (DAS 28>3.2) and low disease activity (DAS 28>2.6) (p<0.01). Serum and SF concentrations of all four cytokines positively correlated with DAS 28 index values, i.e., disease activity. A poor correlation was found for S and SF IL-12 whereas the highest coefficient of correlation was found for SF IL-18 (r=0.879, p<0.01), and SF TNF-alpha (r=0.827, p<0.01) and disease activity in this study. Strong correlation was found between SF TNF-alpha and SF IL-18 levels (r=0.732, p<0.01). In conclusion, SF IL-18 and TNF-alpha levels in RA patients are good indicators of disease activity. The results obtained support the use of the DAS in clinical practice as a reliable method in assessing disease activity in RA patients.
authors.affiliation: Clinic of Rheumatology and Clinical Immunology, Military Medical Academy, Belgrade, Serbia and Montenegro.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Petrovic-Rackov
authors.forename: Nada
authors.initials: N
authors.lastname: Pejnovic
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000097:blood*; D019409:Interleukin-15 / Q000097:blood*; D020382:Interleukin-18 / Q000097:blood*; D008297:Male; D010003:Osteoarthritis / Q000097:blood / Q000276:immunology; D011237:Predictive Value of Tests; D013582:Synovial Fluid / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D019409:Interleukin-15; D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12