Correlation between Serum IL-35 Levels and Bone Loss in Postmenopausal Women with Rheumatoid Arthritis

Abstract

Objective. IL-35 was reported as a crucial anti-inflammatory cytokine and could efficiently regulate bone metabolism in murine collagen-induced arthritis model. However, the relationship between IL-35 and bone health in human rheumatoid arthritis (RA) has not been clarified. In this study, the aim was to explore the correlations between IL-35 and bone loss in postmenopausal women with RA. Methods. The study included 76 postmenopausal women with RA and 53 healthy postmenopausal women as healthy controls (HCs). Serum IL-35 levels were detected by enzyme-linked immunosorbent assay. Bone mineral density (BMD) at lumbar spine 1-4 and at total hip was measured using dual-energy X-ray absorptiometry. Alkaline phosphatase (ALP), β-isomerised carboxy-terminal cross-linking telopeptide of type I collagen (β-CTX), and 25-(OH) VitD3 were measured by turbidimetric inhibition immunoassay. Results. Serum IL-35 levels were increased compared with HCs, and it positively correlated with BMD and 25-(OH) VitD3 and negatively correlated with β-CTX in postmenopausal women with RA. Furthermore, serum IL-35 levels in the increased ALP group were higher than those in the normal ALP group. Conclusions. IL-35, an important anti-inflammatory cytokine, may participate in the pathogenesis of bone loss in postmenopausal women with RA.

Interleukin-35 Is Involved in Angiogenesis/Bone Remodeling Coupling Through T Helper 17/Interleukin-17 Axis

“…However, it has not been fully understood whether IL-35 plays a role in skeletal system. In vivo study, IL-35 was confirmed to be positively correlated with bone mineral density, 25-(OH)VitD3 and be negatively correlated with b-isomerised carboxy-terminal crosslinking telopeptide of type I collagen, suggesting that IL-35 may be involved in the pathogenesis of skeletal system (17). Wanda Niedbala has confirmed that IL-35 can suppress the immune response by regulating the expansion of regular T cells and inhibiting the differentiation of Th17 cells (31).…”

“…In recent years, IL-35 was found to be involved in in multiple inflammatory diseases, autoimmune diseases and cancers, including type I diabetes, hepatitis, non-small cell lung cancer (14)(15)(16). Previous study also reported that IL-35 participated in bone metabolism (17,18). However, the possible mechanisms underlying this function have not been fully understood.…”

Lactococcus lactis as an Interleukin Delivery System for Prophylaxis and Treatment of Inflammatory and Autoimmune Diseases

“…One of the most prominent functions of IL-35 is the ability to propagate infectious tolerance and to generate a potent population of IL-35-expressing regulatory cells, which have been shown to exhibit immunosuppressive activity [ 99 , 100 ]. Functional analysis studies suggested that IL-35 plays a critical role in many autoimmune diseases such as multiple sclerosis (MS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD) [ 101 – 104 ].…”

The Role of IL-35 in the Pathophysiological Processes of Liver Disease

“…IL-35, a newly discovered heterodimeric cytokine and a member of the Interleukin (IL)-12 cytokine family ( Table 1 ) ( Li et al, 2019 ), consists of two subunits: α chain (p35) and β chain (EBI3) ( Kong et al, 2016 ). In detail, p35 had dissociation between p35 and p40 gene regulation ( Skrombolas et al, 2015 ).…”

“…Recent researches have confirmed that IL-35, mainly secreted by immune cells, including the newly reported Breg cells (CD4+CD25+), had a high expression level in the bone marrow, thymus, blood and liver tissues ( Li et al, 2020b ; Zhang et al, 2020 ). Functional analysis suggested that IL-35 played a crucial role in many autoimmune diseases and allograft rejection, such as rheumatoid arthritis (RA) ( Li et al, 2019 ), multiple sclerosis (MS) ( Badihian et al, 2018 ), systemic lupus erythematosus (SLE) ( Ye et al, 2019 ), inflammatory bowel disease (IBD) ( Su et al, 2018 ), psoriasis and experimental autoimmune uveitis (EAU) ( Zhang et al, 2016 ). What’s more, it has been confirmed that IL-35 had a higher expression level in chronic hepatitis patients and its expression level had a positive association with the severity of infection ( Dong et al, 2020 ).…”