Absence of endogenous interleukin-10 enhanced organ dysfunction and mortality associated to zymosan-induced multiple organ dysfunction syndrome.
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.
Malleo
Giuseppe
G
Department of Clinical, Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Torre Biologica, Policlinico Universitario Via C. Valeria, Gazzi, 98100 Messina, Italy.
Mazzon
Emanuela
E
Genovese
Tiziana
T
Di Paola
Rosanna
R
Caminiti
Rocco
R
Esposito
Emanuela
E
Bramanti
Placido
P
Cuzzocrea
Salvatore
S
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
D053583:Interleukin-1beta; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015054:Zymosan