title: 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.
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.
authors.affiliation: Department of Orthopedics, Navy General Hospital, Beijing 100048, China. weilichn@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Centre Laboratory, General Hospital of People's Liberation Army, Beijing 100853, China. tianyiliu08@163.com.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Centre Laboratory, General Hospital of People's Liberation Army, Beijing 100853, China. wuliang080228@163.com.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, Navy General Hospital, Beijing 100048, China. chenchunkk@163.com.
authors.forename: Chun
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Navy General Hospital, Beijing 100048, China. jiazhiweivip@163.com.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Orthopedics, Navy General Hospital, Beijing 100048, China. baixuedongngh@163.com.
authors.forename: Xuedong
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Orthopedics, Navy General Hospital, Beijing 100048, China. ruandikengh@163.com.
authors.forename: Dike
authors.initials: D
authors.lastname: Ruan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007167:Immunotherapy; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D007403:Intervertebral Disc / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D055959:Intervertebral Disc Degeneration / Q000473:pathology / Q000628:therapy; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10