Serum levels of interleukin-6 type cytokines and soluble interleukin-6 receptor in patients with rheumatoid arthritis

Abstract

We investigated the serum concentrations of interleukin-6 (IL-6) and two IL-6 family of cytokines (leukaemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) as well as IL-6 soluble receptor (sIL-6R) using an enzyme-linked immunosorbent assay (ELISA) in 66 patients with rheumatoid arthritis (RA) and 24 healthy controls. We examined a possible association between the serum levels of these peptides and RA activity according to the Mallya and Mace scoring system and Ritchie's index. We also evaluated the correlation between the serum levels of IL-6, LIF, CNTF and sIL-6R and duration of the disease and calculated sIL-6R/IL-6 ratio in RA patients and in the control group. IL-6 and sIL-6R were detectable in all 66 patients with RA and 24 normal individuals. LIF was also found in the serum of all patients with RA and in 16 (66.7%) normal individuals. In contrast CNTF was measurable only in 15 (22.7%) patients with RA and 24 (33.3%) normal individuals. The highest IL-6 and sIL-6R levels were found in the patients with Stages 3 and 4 of RA activity and the lowest in the control group. In contrast there were no statistically significant differences between the LIF and CNTF levels in RA patients and normal individuals. We found positive correlation between IL-6 and sIL-6R concentrations and Ritchie's index and a lack of such correlation with LIF and CNTF. IL-6 serum level correlated positively with the disease duration, but sIL-6R, LIF and CNTF did not. Serum sIL-6R/IL-6 ratio was significantly lower in RA patients than in healthy controls. In conclusion, an increase in the serum levels of IL-6 and sIL-6R, but not LIF and CNTF concentrations, may be useful markers for RA activity.

HepaRG Cells as Human-Relevant In Vitro Model to Study the Effects of Inflammatory Stimuli on Cytochrome P450 Isoenzymes

“…Indeed, plasma concentrations of IL-18 range from around 0.1-0.2 ng/ml in healthy controls but up to 1-2 ng/ml in disease state (Blankenberg et al, 2003;Berke, unpublished observations). IL-6 levels in plasma from nondiseased subjects are typically around 5 pg/ml but can be as high as 50-60 pg/ml in rheumatoid arthritis patients (Robak et al, 1998). Thus, the concentration range used in previous publications of in vitro models extends beyond the values measured in clinical plasma samples, but it is difficult to correlate such measurements to local concentrations in the liver (both IL-6 and IL-18 are locally produced and can act in the tissue), and there is a clear correlation between the in vitro measured effects of IL-6 on P450 and the observations in tocolizumab-treated rheumatoid arthritis patients (Schmitt et al, 2011).…”

RAGE and arthritis: the G82S polymorphism amplifies the inflammatory response

“…To assess the functional consequences of enhanced binding and activation of signal transduction molecules stimulated upon ligation of RAGE by EN-RAGE, we examined production of key inflammatory and tissuedegradative mediators linked to RA [24][25][26] by MPs bearing common or variant RAGE alleles. Exposure of RAGE 82G-bearing MPs to EN-RAGE caused a significant increase in generation of TNF-alpha detected in culture supernatant compared with quiescent cultures (470 ± 53 vs 15 ± 2 pg/ml; P Ͻ 0.001) (Figure 5e).…”

Animal models of rheumatoid arthritis: How informative are they?

“…Ant-IL-17 mAb therapy continues to be explored as a therapy for RA, particularly for anti-TNF nonresponders and in other related autoimmune disorders such as psoriasis and anklosing spondylitis. IL-6 is known to promote Th17 differentiation (Bettelli et al, 2006;Korn et al, 2009) and elevated levels of IL-6 have been found in the synovial fluid of RA patients (Hirano et al, 1988;Houssiau et al, 1988;Robak et al, 1998). The joints of SKG mice have enhanced IL-6 gene expression and protein when compared to BALB/c mice and IL-6 -/-SKG mice are protected from synovitis and joint destruction and fail to produce Th17 cells (Hirota et al, 2007).…”