Clinical significance of IL-18, IL-15, IL-12 and TNF-α 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.

Immunopathological mechanisms in dogs with rupture of the cranial cruciate ligament

“…However, it is now clear that this cytokine also has a function in chronic joint inflammation (Sukedai et al, 2004;Emshoff et al, 2000). High levels of TNF-a are detected by ELISA in the SF of human patients with chronic RA (Isomaki et al, 1996;Lettesjo et al, 1998;Petrovic-Rackov and Pejnovic, 2006). In addition, clinical trials targeting TNF-a (anti-TNF-a antibodies, soluble TNF-a receptors) ameliorate disease symptoms in patients with acute and chronic RA (Brennan et al, 1995;Macias et al, 2005).…”

RANKL Induces IL-18 Binding Protein Expression in RAW264.7 Cells

“…Based on previous studies that reported the stimulatory effect of IL-18 on GM-CSF expression in CD4 + T cells [11][12][13] , we hypothesized that the free IL-18BP in culture supernatants derived from RANKL-treated RAW264. An increase in the level of IL-18 has been observed in the serum or pathological tissue in individuals with rheumatoid arthritis [28][29][30][31] or periodontitis 32,33) , both of which are well-recognized as inflammatory diseases with bone destruction, through RANKLinduced osteoclast formation [34][35][36] . The results in our present study may help explain how RANKL, IL-18 and IL-18BP are involved in the cell-cell interactions between osteoclast precursor cells and CD4 + T cells in these bone-destructive disorders.…”

Cachexia – The Interplay Between the Immune System, Brain Control and Metabolism

“…These findings suggest that IL-15 might represent a new immunomodulatory and anabolic tool for the treatment of cachexia associated with metastatic malignancies (Waldmann et al, 2011). However, the potential application of IL-15 in other conditions associated with inflammatory cachexia syndrome should be carefully evaluated because IL-15 is also proposed as an important factor in pathogenesis of several chronic inflammatory diseases such as rheumatoid arthritis (Petrovic-Rackov & Pejnovic, 2006). Contradictory findings have been obtained in possible involvement of IL-15 in sarcopenia, the degenerative loss of skeletal muscle mass and strength associated with aging, in rats.…”

“…Moreover, particularly IL-6, whose level is dependent on stimulation of TNFand IL-1, predicts mortality in patients with end-stage renal disease (Cheung et al, 2010). In patients with rheumatoid arthritis, the overproduction of TNF-and IL-1 is associated with hypermetabolism and reduced body cell mass, and serum concentrations of these cytokines as well as IL-6, IL-15, IL-18, and IL-12 correlate strongly with disease severity (Roubenoff et al, 1994;Petrovic-Rackov & Pejnovic, 2006;de Paz et al, 2010). Patients with COPD also exhibit an increase in resting energy expenditure and a decrease in free-fat mass, and these patients have markedly increased acute phase reactant proteins and inflammatory factors (IL-8, soluble TNF receptors: sTNF-R55 and sTNF-R75) in their serum (Schols et al, 1996).…”