title: Absence of endogenous interleukin-10 enhanced organ dysfunction and mortality associated to zymosan-induced multiple organ dysfunction syndrome.
abstract: Experimental evidence suggests that interleukin (IL)-10 plays a pivotal role in generalized inflammation. Here we investigate the effects of IL-10 gene deletion on the acute phase of the multiple organ dysfunction syndrome (MODS) caused by zymosan in the mouse. MODS was induced by zymosan administration (500 mg/kg, suspended in saline solution, i.p.) in IL-10 wild-type and knockout mice; sham groups were treated with vehicle. Mice were sacrificed 18 h after zymosan or saline administration. In another set of experiments, animals were monitored for 12 days to assess systemic toxicity and survival rate. Mice lacking IL-10 displayed increased peritoneal exudate volume and leukocytes. Also, we observed a significant increase in myeloperoxidase activity and lipid peroxidation in ileum and lung tissues, as well as augmented levels of TNF-alpha, IL-1beta and nitrogen-derived species in the plasma. With regard to organ injury, absence of IL-10 enhanced the renal, hepatocellular and pancreatic dysfunction caused by zymosan administration. All of these parameters significantly influenced the systemic toxicity and the overall survival at 12 days, which was significantly lower in IL-10 knockout mice. Therefore, this study demonstrates that the absence of endogenous IL-10 enhances the MODS induced by zymosan in mice.
authors.affiliation: Department of Clinical, Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Torre Biologica, Policlinico Universitario Via C. Valeria, Gazzi, 98100 Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Malleo
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Tiziana
authors.initials: T
authors.lastname: Genovese
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Rocco
authors.initials: R
authors.lastname: Caminiti
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000818:Animals; D017353:Gene Deletion; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D053583:Interleukin-1beta / Q000097:blood; D007668:Kidney / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009102:Multiple Organ Failure / Q000139:chemically induced / Q000503:physiopathology*; D020556:Neutrophil Infiltration; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D010179:Pancreas / Q000503:physiopathology; D010538:Peritonitis / Q000139:chemically induced; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015054:Zymosan / Q000633:toxicity
chemical_list: D053583:Interleukin-1beta; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015054:Zymosan