IL-37 is associated with osteoarthritis disease activity and suppresses proinflammatory cytokines production in synovial cells

Abstract

The objective of this study is to investigate the correlation between IL-37 level and osteoarthritis activity and to determine the anti-inflammatory effects of IL-37 in peripheral blood mononuclear cells (PBMCs) and synovial cells (SCs) from osteoarthritis (OA) patients, which including 32 patients with erosive inflammatory OA (EIOA) and 40 patients with primary generalized OA (PGOA), 40 age and sex matched healthy volunteers were recruited as healthy controls (HCs). The protein and relative mRNA levels of IL-37 were significant increased in the blood of EIOA patients compared with those of PGOA patients and HCs. Serum IL-37 levels of OA patients were positively correlated with VAS score, as well as with CRP, ESR in blood. Positive correlations were also observed among IL-37 with IL-1β, TNF-α and IL-6 in synovial cells. Furthermore, the expression of IL-1β, TNF-α and IL-6 in PBMCs and SCs from EIOA patients was suppressed by IL-37 in vitro. In conclusion, our results indicated that IL-37 increased in EIOA patients and was positively correlated with disease activity, the pro-inflammatory cytokines such as IL-1β, TNF-α and IL-6 in PBMCs and synovial cells from EIOA patients were restrained by recombinant IL-37. Thus, IL-37 may serve as a novel therapeutic target for the treatment of OA inflammation.

Figure 1

Comparison of IL-37 mRNAs and protein levels between OA and HC. Expression of IL-37 mRNAs in PBMCs from primary generalized OA (n = 40), erosive inflammatory OA (n = 32) OA patients and HCs (n = 40) was detected by RT-PCR (a). Serum IL-37 protein levels were determined by ELISA (b). Each symbol represents an individual OA patient and HC. The results are presented as mean ± SD.

Figure 2

Correlations of serum IL-37 levels with OA clinical values. Each symbol represents an individual OA patient. Serum IL-37 levels in OA were positively correlated with VAS (a), CRP (b) and ESR (c). The correlations were evaluated with Spearman’s non-parametric test.

Figure 3

IL-37 suppresses the expression of pro-inflammatory cytokines in PBMCs from EIOA patients. The mRNAs expression of TNF-α (a), IL-1β(b) and IL-6 (c) in PBMCs from EIOA patients (n = 32) and HCs (n = 40) were analyzed by RT-PCR, the supernatants produced by PBMCs were collected for measuring TNF-α(d), IL-1β (e) and IL-6 (f) protein levels by ELISA.

Figure 4

Comparison of IL-37 mRNAs and protein levels between PBMCs and Synovial cells (SCs) from EIOA patients. PBMCs and SCs were collected from EIOA patients (n = 12). the relative mRNA (a) and protein levels (b) were detected by RT-PCR and ELISA, respectively.

Figure 5

Correlation between IL-37 and pro-inflammatory cytokines in synovial cells from EIOA patients. Synovial IL-37 levels were positively correlated with TNF-α (a), IL-1β (b), and IL-6 (c) produced by SCs from EIOA patients (n = 12). Each symbol indicates an individual patient.

Figure 6

IL-37 inhibits the expression of inflammatory cytokines in synovial cells from EIOA patients. Synovial cells isolated from synovial tissues of EIOA patients (n = 12) were treated similarly to the PBMCs. The relative mRNA expression of TNF-α (a), IL-1β (b) and IL-6 (c) were analyzed by RT-PCR, the protein levels of these cytokines produced by SCs were analyzed by ELISA (d–f).