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| Author(s): |
Dennys Esper Cintra
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas |
| Defense date: | 2008-04-12 |
| Examining board members: |
Licio Augusto Velloso;
Tania Cristina Pithon Curi;
Jacqueline Pontes Monteiro;
Marcio Alberto Torsoni;
Everardo Magalhães Carneiro
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| Advisor: | Licio Augusto Velloso |
| Abstract | |
Obesity has grown as an epidemiological phenomenon that threatens millions of people worldwide, and particularly those living in western, developed countries. Besides its multiple behavioral and social problems, obesity contributes considerably to increase morbidity and mortality due to its common association with diseases that compose the metabolic syndrome, such as diabetes mellitus, hypertension, dyslipidemia, polycystic ovaries, hepatic steatosis, among others. The abnormalities in the metabolism of fatty acids that frequently occur in obesity, contribute to the dysfunction of a number of organs and systems. In the liver, the simple accumulation of fat in the parenchyma cells leads to steatosis which is somewhat benign and reversible. However, as far as the condition is maintained, and depending on some yet to be known genetic factors, an inflammatory response can be installed leading to steatohepatitis, fibrosis and cirrhosis, a terminal liver disease. During the installation of steatohepatitis, a number of proinflammatory cytokines are expressed, contributing to the progression of the liver damage. However, some recent studies have shown that interleukin-10 (IL- 10), an anti-inflammatory cytokine, is produced in the liver and plays a role in the negative modulation of the inflammatory response. The objective of the present study was to evaluate the roles of IL-10 as an endogenous factor controlling inflammatory and metabolic parameters in diet induced hepatic steatosis. IL-10 was inhibited in vivo by two distinct methods, a neutralizing antibody and an antisense oligonucleotide. The inhibition of IL-10 in diet induced steatohepatitis increased proinflammatory cytokine expression and worsened a number of metabolic parameters, including insulin signal transduction. Thus, IL-10 is an endogenous factor that modulates inflammatory response in diet-induced hepatic disease. (AU) | |