title: Spleen-derived interleukin-10 downregulates the severity of high-fat diet-induced non-alcoholic fatty pancreas disease.
abstract: Obesity is associated with systemic low-grade inflammation and is a risk factor for non-alcoholic fatty pancreas disease (NAFPD), but the molecular mechanisms of these associations are not clear. Interleukin (IL)-10, a potent anti-inflammatory cytokine, is released during acute pancreatitis and is known to limit inflammatory responses by downregulating the release of proinflammatory mediators. The origin of IL-10 that suppresses pancreatitis has not been investigated. Since obesity is known to reduce expression of proinflammatory cytokines in the spleen, we examined whether spleen-derived IL-10 regulates NAFPD caused by high-fat (HF) diet-induced obesity. The following investigations were performed: 1) IL-10 induction from spleen was examined in male mice fed a HF diet; 2) triglyceride content, expression of pro- and anti-inflammatory cytokines and infiltration of M1 and M2 macrophages were determined to evaluate ectopic fat accumulation and inflammatory responses in the pancreas of splenectomy (SPX)-treated mice fed HF diet; 3) exogenous IL-10 was systemically administered to SPX-treated obese mice and the resulting pathogenesis caused by SPX was assessed; and 4) IL-10 knockout (IL-10KO) mice were treated with SPX and ectopic fat deposition and inflammatory conditions in the pancreas were investigated. Obesity impaired the ability of the spleen to synthesize cytokines, including IL-10. SPX aggravated fat accumulation and inflammatory responses in the pancreas of HF diet-induced obese mice and these effects were inhibited by systemic administration of IL-10. Moreover, SPX had little effect on fat deposition and inflammatory responses in the pancreas of IL-10KO mice. Our findings indicate that obesity reduces IL-10 production by the spleen and that spleen-derived IL-10 may protect against the development of NAFPD.
authors.affiliation: Department of Internal Medicine 1, Faculty of Medicine, Oita University, Yufu City, Oita, 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: Kentaro
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Masaki
authors.forename: Seiichi
authors.initials: S
authors.lastname: Chiba
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Mitsutomi
authors.forename: Takanobu
authors.initials: T
authors.lastname: Shimasaki
authors.forename: Hisae
authors.initials: H
authors.lastname: Ando
authors.forename: Kansuke
authors.initials: K
authors.lastname: Fujiwara
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: Toshiie
authors.initials: T
authors.lastname: Sakata
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yoshimatsu
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D015536:Down-Regulation / Q000187:drug effects; D005355:Fibrosis / Q000209:etiology; D016753:Interleukin-10 / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000150:complications / Q000209:etiology / Q000378:metabolism; D010182:Pancreatic Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D010195:Pancreatitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D012720:Severity of Illness Index; D013154:Spleen / Q000378:metabolism* / Q000601:surgery; D013156:Splenectomy / Q000009:adverse effects
chemical_list: D016753:Interleukin-10