Hyperleptinemia suppresses aggravation of arthritis of collagen-antibody-induced arthritis in mice

• Published in: Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 2015-11, Vol.20 (6), p.1106-1113
• Main Authors: Okano, Tadashi, Koike, Tatsuya, Tada, Masahiro, Sugioka, Yuko, Mamoto, Kenji, Inui, Kentaro, Okihana, Hiroyuki, Ebihara, Ken, Nakao, Kazuwa, Nakamura, Hiroaki
• Format: Article
• Language: English
• Subjects: Animals; Arthritis, Experimental - blood; Arthritis, Experimental - pathology; Arthritis, Experimental - physiopathology; Biopsy, Needle; Cartilage, Articular - physiopathology; Collagen Type II - pharmacology; Cytokines - analysis; Cytokines - metabolism; Disease Models, Animal; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Immunohistochemistry; Interleukin-6 - metabolism; Leptin - blood; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Mice, Transgenic; Original Article; Orthopedics; Random Allocation; Real-Time Polymerase Chain Reaction - methods; Rheumatology; Sensitivity and Specificity
• ISSN: 0949-2658; 1436-2023
• DOI: 10.1007/s00776-015-0768-7

Leptin is an adipocytokine produced by adipocytes and controlling body weight. It is unclear whether leptin works as a proinflammatory or an anti-inflammatory cytokine. We investigated the effects of hyperleptinemia on leptin transgenic (LepTg) mice in terms of cartilage destruction, bone destruction, joint synovitis, and serum cytokine levels by using a mouse model of collagen-antibody-induced arthritis (CAIA). CAIA was induced for female age-matched 6- to 8-week-old C57BL/6J control mice and LepTg mice. Mice were injected intraperitoneally with 5mg of a combination of monoclonal antibody specific for type II collagen on day 0 and 12.5mg of lipopolysaccharide (LPS) on day 3. Clinical evaluation of arthritis was monitored for 14days, and hind paws were examined clinically and histologically. Serum cytokine levels of interleukin (IL)-1β, IL-6, IL-10, and IL-17 and tumor necrosis factor alpha (TNF-α) were also analyzed on days 0 and 5. Moreover, THP-1 cells, which are human monocytic cell line derived from an acute monocytic leukemia patient, were cultured and differentiated into macrophages. The effects of leptin on messenger RNA (mRNA) expression of IL-6 were examined by real-time quantitative polymerase chain reaction (RT-PCR). Serum leptin concentrations were approximately ninefold higher in LepTg mice (62.0±20.7ng/ml) than in control mice (7.2±0.5ng/ml). Severity of clinical paw swelling, arthritis score, synovial hyperplasia, and cartilage damage were suppressed in LepTg mice with CAIA. Although serum cytokine levels of IL-1β, IL-17, and IL-10 and TNF-α showed no significant changes in two mice, serum levels of IL-6 in LepTg mice were suppressed at day 5. Moreover, in vitro study showed that IL-6 elevation following LPS exposure in THP-1 cells was suppressed with high leptin concentrations. Our finding suggests that hyperleptinemia suppress IL-6 responses and progression of joint inflammation. Leptin may play an anti-inflammatory role under hyperleptinemia.