title: IL-20 contributes to low grade inflammation and weight gain in the Psammomys obesus.
abstract: The metabolic syndrome has been demonstrated in gene deficient animals, e.g. db/db mice, to include a systemic inflammation leading to insulin resistance, obesity and type 2 diabetes (T2D). To determine the importance of inflammation in obesity and diabetes, in a normal non-genetically modified species, an intervention study with neutralizing anti-IL-20 antibodies was conducted in the spontaneous T2D model Psammomys obesus. All IL-20 receptor chains were expressed on protein level in the Psammomys obesus. Neutralization of IL-20 did not modulate blood glucose, HbA1c, insulin levels or lymphocyte numbers after five weeks treatment although a trend to reduced weight gain rate was observed upon anti-IL-20 treatment. Inhibition of IL-20 significantly increased the number of CD11bhigh/lowcells and the CD11bGr-1intmyeloid derived suppressor cells in the spleen. Importantly, although the number of M1-like monocytes remained unchanged the M1-like marker CD11c expression level was reduced on the cells upon anti-IL-20 treatment. Anti-IL-20 treatment reduced both TLR4 and CCR2b expression on the macrophages upon treatment. Further, a marked shift in the protein signature in the pancreatic tissue after anti-IL-20 treatment was observed including enhanced expression of CXCL12, TIMP-1 and IL-10 while IL-1β, CXCL4, PEDF and ADAMTS1 were reduced. In conclusion, we describe for the first time the systemic immune response in the diabetic Psammomys obesus. Neutralizing IL-20 modulated the myeloid compartment, the adaptive immunity, and local expression of proteins in the diabetic pancreatic tissue as well as improved on weight gain and hence may place IL-20 as a cytokine to be considered in obesity.
authors.affiliation: Hagedorn Research Institute, DK-2820 Gentofte, Denmark.
authors.forename: Helena
authors.initials: H
authors.lastname: Cucak
authors.affiliation: Hagedorn Research Institute, DK-2820 Gentofte, Denmark.
authors.forename: Lise
authors.initials: L
authors.lastname: Høj Thomsen
authors.affiliation: Hagedorn Research Institute, DK-2820 Gentofte, Denmark. Electronic address: alexander.rosendahl.axrd@gmail.com.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rosendahl
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019138:Antibodies, Blocking / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology* / Q000628:therapy; D005849:Gerbillinae / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000628:therapy; D018836:Inflammation Mediators / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D000072737:Myeloid-Derived Suppressor Cells / Q000187:drug effects / Q000276:immunology*; D009765:Obesity / Q000276:immunology* / Q000628:therapy; D010179:Pancreas / Q000187:drug effects / Q000276:immunology*; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
chemical_list: D019138:Antibodies, Blocking; D018836:Inflammation Mediators; D007328:Insulin; D007378:Interleukins; D018123:Receptors, Interleukin; C492510:interleukin-20 receptor; C422042:interleukin 20
keywords: Cytokines; Diabetes; Inflammation; Lymphocytes; Obesity; Pre-clinical