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Role of the splashnic nerve in immune regulation in a septic peritonitis model

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Author(s):
Gabriela Carvalho Santos Ferreira
Total Authors: 1
Document type: Master's Dissertation
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Alexandre Alarcon Steiner; Jose Alexandre Marzagao Barbuto; Luiz Guilherme de Siqueira Branco; Vinícius Nunes Cordeiro Leal
Advisor: Alexandre Alarcon Steiner; Flávio Vieira Loures
Abstract

It is known that autonomic nerves regulate the immune system. But although the roles of the vagus nerve in immunoregulation have been extensively investigated, there is scant information about the roles played by sympathetic nerves. Here, we have assessed whether and how the sympathetic splanchnic nerves regulate host defense in a rat model of peritonitis. Bilateral splanchnic denervation (SplancX) or sham surgery was performed one week before the E. coli challenge. The challenge consisted of an E. coli -enriched gauze implanted in the peritoneum. Bacterial burden, leukocyte infiltration and organ-injury markers were assessed. Bacterial burden was the highest in the primary site of infection (peritoneum), followed by the spleen and lungs. Compared to the sham-operated rats, the SplancX rats were more efficient at clearing bacteria in the spleen and the primary site of infection when E. coli was given at the dose of 1x104/rat. However, when E. coli was given at a higher dose 1x106/rat, SplancX reduced bacterial burden only in the spleen. Effectiveness of the immune system in the SplancX rats was not promoted by enhanced migration of leukocytes, as the groups did not differ in relation to the numbers of CD45+/RP1+/CD68- cells (neutrophils) or CD45+/RP1-/CD68+ cells (macrophages) in peritoneum, lungs, or spleen. Enhancement of microbicidal mechanisms of neutrophils or macrophages are possibly involved. We hypothesized that augmented microbicidal activity could come with the cost of enhanced collateral damage of organs. However, the results revealed that, compared to Sham surgery, SplancX did not increase the levels of established organ-injury markers. It should be considered, though, that the levels of such markers were not well above refence values in the timeframe of the experiment (24 h). The data uncover a suppressive role of the splanchnic nerves on bacterial clearance. This role was not related to changes in the infiltration of tissues by neutrophils and macrophages within 24 h of infection. Changes in the microbicidal activity of these leukocytes are presumably involved. Improved bacterial clearance in the absence of the splanchnic nerves did not result in augmented collateral damage, but such costs might become evidence in other contexts, such as prolonged infection. (AU)

FAPESP's process: 19/26164-6 - Thermal regulation of acquired immune response against Paracoccidioides brasiliensis
Grantee:Gabriela Carvalho Santos Ferreira
Support Opportunities: Scholarships in Brazil - Master