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Comparison of activation of the pineal-immune axis between lethal and non-lethal systemic inflammatory processes

Grant number: 16/26081-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2017
Effective date (End): December 31, 2017
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Pedro Augusto Carlos Magno Fernandes
Grantee:Leandro Tetsuo Mori
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The melatonin produced by the pineal gland during the dark stage of the environment controls the endogenous oscillatory system of mammals, adjusting the activity of various organs, tissues and cells. Nocturnal melatonin decreases, for example, the expression of vascular endothelial adhesion molecules by reducing the migration of immunocompetent cells between the circulation and tissues. During the assembly of inflammatory responses, neuroimmunoendocrine mediators block the synthesis of melatonin by the pineal, facilitating the migration of leukocytes to the injured site. In addition to synthesis by the pineal gland, the extra-pineal production of melatonin locally regulates physiological and pathophysiological processes. During defense responses, melatonin produced by lymphocytes and macrophages modulates the production of leukocyte cytokines and increases the phagocytic capacity of macrophages. In this way, adequate assembly of defense processes is adjusted by the temporal shift of melatonin producing sources. On the other hand, deregulated inflammatory responses can lead to death and little is known about the activation of this pineal-immune axis in these contexts. In this project, we will compare the activation of the pineal-immune axis (inhibition / stimulation of melatonin production by pineal and immunocompetent cells) in rats injected with lethal and non-lethal doses of LPS. Our hypothesis is that the activation profile of this axis in lethal situations is altered and that the modulation of the melatonergic system will increase the survival of the animals injected with lethal doses of LPS. (AU)