title: Hyperleptinemia suppresses aggravation of arthritis of collagen-antibody-induced arthritis in mice.
abstract: BACKGROUND
  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).
  
  
  METHODS
  CAIA was induced for female age-matched 6- to 8-week-old C57BL/6 J control mice and LepTg mice. Mice were injected intraperitoneally with 5 mg of a combination of monoclonal antibody specific for type II collagen on day 0 and 12.5 mg of lipopolysaccharide (LPS) on day 3. Clinical evaluation of arthritis was monitored for 14 days, 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).
  
  
  RESULTS
  Serum leptin concentrations were approximately ninefold higher in LepTg mice (62.0 ± 20.7 ng/ml) than in control mice (7.2 ± 0.5 ng/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.
  
  
  CONCLUSIONS
  Our finding suggests that hyperleptinemia suppress IL-6 responses and progression of joint inflammation. Leptin may play an anti-inflammatory role under hyperleptinemia.
authors: Department of Orthopaedic Surgery, Osaka City University Medical School, 1-4-3 Asahi-machi Abeno-ku, Osaka, 545-8585, Japan.
authors: Tadashi
authors: T
authors: Okano
authors: Center for Senile Degenerative Disorders (CSDD), Osaka City University Medical School, 1-4-3 Asahi-machi Abeno-ku, Osaka, 545-8585, Japan. tatsuya@med.osaka-cu.ac.jp.|Search Institute for Bone and Arthritis Disease (SINBAD), Shirahama Health and Welfare Foundation, 1447 Shirahama-cho, Nishimuro-gun, Wakayama, 649-2211, Japan. tatsuya@med.osaka-cu.ac.jp.
authors: Tatsuya
authors: T
authors: Koike
authors: Department of Orthopaedic Surgery, Osaka City University Medical School, 1-4-3 Asahi-machi Abeno-ku, Osaka, 545-8585, Japan.
authors: Masahiro
authors: M
authors: Tada
authors: Center for Senile Degenerative Disorders (CSDD), Osaka City University Medical School, 1-4-3 Asahi-machi Abeno-ku, Osaka, 545-8585, Japan.
authors: Yuko
authors: Y
authors: Sugioka
authors: Department of Orthopaedic Surgery, Osaka City University Medical School, 1-4-3 Asahi-machi Abeno-ku, Osaka, 545-8585, Japan.
authors: Kenji
authors: K
authors: Mamoto
authors: Department of Orthopaedic Surgery, Osaka City University Medical School, 1-4-3 Asahi-machi Abeno-ku, Osaka, 545-8585, Japan.
authors: Kentaro
authors: K
authors: Inui
authors: Center for Senile Degenerative Disorders (CSDD), Osaka City University Medical School, 1-4-3 Asahi-machi Abeno-ku, Osaka, 545-8585, Japan.
authors: Hiroyuki
authors: H
authors: Okihana
authors: Translational Research Center, Kyoto University Hospital, Kyoto University School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors: Ken
authors: K
authors: Ebihara
authors: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicne, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors: Kazuwa
authors: K
authors: Nakao
authors: Department of Orthopaedic Surgery, Osaka City University Medical School, 1-4-3 Asahi-machi Abeno-ku, Osaka, 545-8585, Japan.
authors: Hiroaki
authors: H
authors: Nakamura
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood* / Q000473:pathology* / Q000503:physiopathology; D001707:Biopsy, Needle; D002358:Cartilage, Articular / Q000503:physiopathology*; D024043:Collagen Type II / Q000494:pharmacology; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism; D020738:Leptin / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity
chemical_list: D024043:Collagen Type II; D016207:Cytokines; D015850:Interleukin-6; D020738:Leptin