Blocking the function of inflammatory cytokines and mediators by using IL-10 and TGF-β: a potential biological immunotherapy for intervertebral disc degeneration in a beagle model.

Wei Li,Xuedong Bai,Zhiwei Jia,Chun Chen,Liangliang Wu,Dike Ruan,Tianyi Liu

doi:10.3390/ijms151017270

Abstract

The debilitating effects of lower back pain are a major health issue worldwide. A variety of factors contribute to this, and oftentimes intervertebral disk degeneration (IDD) is an underlying cause of this disorder. Inflammation contributes to IDD, and inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, play key roles in the pathology of IDD. Therefore, the development of treatments that inhibit the expression and/or effects of TNF-α and IL-1β in IDD patients should be a promising therapeutic approach to consider. This study characterized the potential to suppress inflammatory cytokine production in degenerative intervertebral disc (NP) cells by treatment with IL-10 and TGF-β in a canine model of IDD. IDD was induced surgically in six male beagles, and degenerative NP cells were isolated and cultured for in vitro studies on cytokine production. Cultured degenerative NP cells were divided into four experimental treatment groups: untreated control, IL-10-treated, TGF-β-treated, and IL-10- plus TGF-β-treated cells. Cultured normal NP cells served as a control group. TNF-α expression was evaluated by fluorescence activated cell sorting (FACS) analysis and enzyme-linked immunosorbent assay (ELISA); moreover, ELISA and real-time PCR were also performed to evaluate the effect of IL-10 and TGF-β on NP cell cytokine expression in vitro. Our results demonstrated that IL-10 and TGF-β treatment suppressed the expression of IL-1β and TNF-α and inhibited the development of inflammatory responses. These data suggest that IL-10 and TGF-β should be evaluated as therapeutic approaches for the treatment of lower back pain mediated by IDD.

Highlights

Debilitating lower back pain (LBP) is a significant medical problem for over half of the adult population worldwide [1]
We evaluated the potential of IL-10 and transforming growth factor (TGF)-β to inhibit the release of tumor necrosis factor (TNF)-α and IL-1β from degenerative nucleus pulposus (NP) cells to determine if combining these two biologics might be a promising approach for the treatment of intervertebral disc degeneration (IDD)
After 24 h, the mean fluorescence intensity (MFI) values for TNF-α in the normal NP cells group and all three treatment groups were significantly lower (p < 0.01) relative to untreated degenerative NP cells. Treatment with both IL-10 and TGF-β resulted in significantly lower TNF-α expression (p < 0.01) than treatment with TGF-β or IL-10 alone (Figure 1C), and TNF-α levels were similar to levels observed in the normal NP cells group

Summary

Introduction

Debilitating lower back pain (LBP) is a significant medical problem for over half of the adult population worldwide [1]. A key factor that contributes to LBP is intervertebral disc degeneration (IDD), which can result in debilitating pain and reduce the quality of life for LBP patients as well as inflicting significant financial burdens due to lost productivity and increased health care costs [2,3]. Effective clinical management of LBP caused by IDD is challenging, because the exact mechanism of IDD is still unclear, and current therapies for LBP caused by IDD only address symptomatic relief for the patient and not the underlying cause of the disease [4]. IDD are needed to enable the development of effective disease-modifying therapies that block the biochemical and pathophysiologic processes mediating this degeneration [5,6].

Results

Discussion

Conclusion