title: Obesity-related chronic kidney disease is associated with spleen-derived IL-10.
abstract: BACKGROUND
  Obesity is associated with systemic low-grade inflammation and is a risk factor for chronic kidney disease (CKD), but the molecular mechanism remains uncertain. We noticed spleen-derived interleukin (IL)-10 because it is observed that obesity reduces several cytokines in the spleen.
  
  
  METHODS
  We examined whether spleen-derived IL-10 regulates CKD caused by a high-fat diet (HF)-induced obesity as follows: (i) male mice were fed with HF (60% fat) during 8 weeks and IL-10 induction from the spleen was examined, (ii) glomerular hypertrophy, fibrosis, inflammatory responses in the kidney and systolic blood pressure (SBP) were evaluated in splenectomy (SPX)-treated mice fed HF, (iii) exogenous IL-10 was systemically administered to HF-induced obese mice and the alteration of obesity-induced pathogenesis caused by IL-10 treatment was assessed. (iv) IL-10 knockout (IL-10KO) mice were treated with SPX and glomerular hypertrophy, fibrosis and the inflammatory condition in the kidney and SBP were also investigated.
  
  
  RESULTS
  Obesity decreased serum levels of only IL-10, an anti-inflammatory cytokine even though pro- and anti-inflammatory cytokine expression in the spleen was significantly lower in the obese group. SPX aggravated HF-induced inflammatory responses in the kidney and hypertension. These HF-induced alterations were inhibited by systemically administered IL-10. Moreover, SPX had little effect on inflammatory responses and SBP in the kidney of IL-10KO mice.
  
  
  CONCLUSIONS
  We suggest that obesity reduces IL-10 induction from the spleen, and spleen-derived IL-10 may protect against the development of CKD induced by obesity.
authors.affiliation: Department of Internal Medicine 1, Faculty of Medicine, Oita University, Hasama, Yufu, Japan. gotokoro@oita-u.ac.jp
authors.forename: Koro
authors.initials: K
authors.lastname: Gotoh
authors.forename: Megumi
authors.initials: M
authors.lastname: Inoue
authors.forename: Takayuki
authors.initials: T
authors.lastname: Masaki
authors.forename: Seiichi
authors.initials: S
authors.lastname: Chiba
authors.forename: Kentaro
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Takanobu
authors.initials: T
authors.lastname: Shimasaki
authors.forename: Kazue
authors.initials: K
authors.lastname: Matsuoka
authors.forename: Hisae
authors.initials: H
authors.lastname: Ando
authors.forename: Kansuke
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Naoya
authors.initials: N
authors.lastname: Fukunaga
authors.forename: Kohei
authors.initials: K
authors.lastname: Aoki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nawata
authors.forename: Isao
authors.initials: I
authors.lastname: Katsuragi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kakuma
authors.forename: Masataka
authors.initials: M
authors.lastname: Seike
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yoshimatsu
mesh_terms: D000818:Animals; D001795:Blood Pressure Determination; D015153:Blotting, Western; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016753:Interleukin-10 / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000150:complications* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D051436:Renal Insufficiency, Chronic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism* / Q000473:pathology; D013156:Splenectomy
chemical_list: D016207:Cytokines; C556062:IL10 protein, mouse; D012333:RNA, Messenger; D016753:Interleukin-10