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Hypothermia in Sepsis: causes and consequences

Grant number: 18/03418-0
Support type:Research Projects - Thematic Grants
Duration: October 01, 2018 - September 30, 2023
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Alexandre Alarcon Steiner
Grantee:Alexandre Alarcon Steiner
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:André Fujita ; Chao Yun Irene Yan ; Flávio Vieira Loures ; Luiz Antonio Baccalá ; Marcelo Nicolas Muscara ; Niels Olsen Saraiva Câmara ; Norberto Peporine Lopes ; Thiago dos Santos Moreira ; Vera Lucia Garcia Calich ; William Tadeu Lara Festuccia ; Wilson Araújo da Silva Junior
Associated grant(s):19/01944-9 - Multi-User Equipment approved in grant 2018/03418-0: Oxylite System, AP.EMU
Associated scholarship(s):20/09399-7 - Development of hypothermia in systemic inflammation: the brain hypoxia hypothesis, BP.PD
19/26164-6 - Thermal regulation of acquired immune response against Paracoccidioides brasiliensis, BP.MS
20/00631-4 - Development of hypothermia in systemic inflammation: the signaling hypothesis cryogenic, BP.DD
+ associated scholarships 19/16851-6 - Thermal modulation of antigen presenting cells interaction with T lymphocytes, BP.TT
19/11818-0 - Thermal modulation of lymphocyte function in P. brasiliensis infection, BP.TT
19/12032-0 - Thermal modulation of the dendritic cell profile in P. brasiliensis infection, BP.IC
17/13350-0 - The temperature negatively regulates the microbicidal activity of macrophages: why do they kill more in hypothermia?, BP.PD
18/21521-2 - Thermal modulation of lung function in P. brasiliensis infection, BP.IC - associated scholarships

Abstract

Sepsis (systemic inflammation in the setting of infection) is a leading cause of mortality in Brazil and worldwide. A switch in thermal state from fever to hypothermia occurs in the most severe cases of Sepsis, which has led to the perception that hypothermia reflects organ failure and is detrimental. We argue that this perception may be premature and incorrect, since there is evidence indicating that such hypothermia is a regulated phenomenon that aids the infected host better than fever in the most severe cases of Sepsis. However, in spite of this evidence, the mechanisms involved remain unknown. Here, we propose to study the causes and consequences of hypothermia in experimental models of systemic inflammation and Sepsis. In specific aim I, we will test the hypothesis that, during systemic inflammation, a discrete fall in regional blood flow to the brain triggers reflex inhibition of the sympathetic drive to brown fat thermogenesis, which consequently promotes the switch from fever to hypothermia. In specific aim II, we will employ phenotype-specific gene deletions to unravel the mechanisms by which the constitutive isoform of cyclooxygenase (COX-1) in the spleen and other peripheral tissues contributes to the development of hypothermia in acute systemic inflammation. In specific aim III, we will conduct experiments to elucidate the mechanisms underlying the opposite effects that a switch from fever-like to hypothermia-like temperatures exerts on the microbicidal actions of neutrophils versus macrophages, thus reprogramming the innate immune response. In specific aim IV, we will investigate whether and how hypothermia can be a burden for the development of acquired, lymphocyte-dependent immune responses, despite its benefits during the acute phase of systemic inflammation. (AU)

Matéria(s) publicada(s) na Agência FAPESP sobre o auxílio:
Novel approach to understanding of immune system could lead to personalized therapy against sepsis  
Novel approach to understanding of immune system could lead to personalized therapy against sepsis  
Articles published in other media outlets (29 total):
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UOL: Em estágios iniciais da covid-19, febre pode ser aliada contra a doença (19/Oct/2020)
UOL: Combinação de febre e hipotermia pode ajudar a combater a sepse (30/Jan/2020)
Sempre Família: Tratar febre no início da Covid-19 dificulta imunidade de rebanho, diz pesquisador (02/Nov/2020)
Câmara Municipal de São Paulo: Capital fecha a quarta-feira com 13,3 mil mortes e 352,9 mil casos confirmados de Covid-19 (22/Oct/2020)
Saber Atualizado: Cientista da USP critica o combate à febre em estágios iniciais da COVID-19 (21/Oct/2020)
NE10: Em estágios iniciais da covid-19, febre pode ser grande aliada contra a doença, afirma estudo (19/Oct/2020)
Jornal da Ciência online: Em estágios iniciais da covid-19, febre pode ser grande aliada contra a doença, afirma estudo (19/Oct/2020)
Agora RN online: Em estágios iniciais da Covid-19, febre pode ser grande aliada contra a doença (19/Oct/2020)
Revista Pará: Em estágios iniciais da Covid-19, febre pode ser grande aliada contra a doença (19/Oct/2020)
ABIPTI - Associação Brasileira das Instituições de Pesquisa Tecnológica e Inovação: Artigo questiona combate à febre em estágios iniciais da COVID-19 (19/Oct/2020)
Portal da Enfermagem: Em estágios iniciais da COVID-19, febre pode ser grande aliada contra a doença, afirma estudo (19/Oct/2020)
Saber Atualizado: Cientistas Brasileiros propõem nova teoria relacionando febre e hipotermia (01/Feb/2020)
Espaço Ecológico no Ar: Combinação de febre e hipotermia pode ajudar a combater a sepse (31/Jan/2020)
Sitios Fuente (México): Revelan por qué una cepa bacteriana es una amenaza en muchos países pero no en Brasil (31/Jan/2020)
Planeta Universitário: Combinação de febre e hipotermia pode ajudar a combater a sepse (30/Jan/2020)
Blog Jornal da Mulher: Combinação de febre e hipotermia pode ajudar a combater a sepse (30/Jan/2020)
Portal da Enfermagem: Combinação de febre e hipotermia pode ajudar a combater a sepse (30/Jan/2020)
Central das Notícias: Combinação de febre e hipotermia pode ajudar a combater a sepse (30/Jan/2020)
Brasil CT&I: Combinação de febre e hipotermia pode ajudar a combater a sepse (30/Jan/2020)
Infosalus (Espanha): Un nuevo enfoque del sistema inmune podría llevar a una terapia personalizada contra la sepsis, según un estudio (29/Jan/2020)
Medindia (Índia): New Approach to Treat Sepsis Discovered (28/Jan/2020)
Bajaprogofficial.com: Novel approach to immune system could lead to personalized therapy against sepsis (26/Jan/2020)
News Medical (Austrália): Combination of two immune defense strategies could afford alternative approach to treating sepsis (23/Jan/2020)
Medical Xpress (Reino Unido): Novel approach to immune system could lead to personalized therapy against sepsis (23/Jan/2020)
Science Codex: Novel approach to immune system could lead to personalized therapy against sepsis (23/Jan/2020)
Scienmag Science Magazine (Reino Unido): Novel approach to immune system could lead to personalized therapy against sepsis (23/Jan/2020)
Healthcare: Novel Approach to Immune System Could Lead to Personalized Therapy Against Sepsis (23/Jan/2020)
My Pharmacy News: Novel approach to immune system could lead to personalized therapy against sepsis (23/Jan/2020)
Hekim.pro Professional Doctors (Azerbaijão): Novel approach to immune system could lead to personalized therapy against sepsis (23/Jan/2020)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CARVALHO, VANESSA F. M.; SALATA, GIOVANNA C.; DE MATOS, JENYFFER K. R.; COSTA-FERNANDEZ, SANDRA; CHORILLI, MARLUS; STEINER, ALEXANDRE A.; DE ARAUJO, GABRIEL L. B.; SILVEIRA, EDILBERTO R.; COSTA-LOTUFO, V, LETICIA; LOPES, LUCIANA B. Optimization of composition and obtainment parameters of biocompatible nanoemulsions intended for intraductal administration of piplartine (piperlongumine) and mammary tissue targeting. International Journal of Pharmaceutics, v. 567, AUG 15 2019. Web of Science Citations: 2.
KOMEGAE, EVILIN N.; FONSECA, MONIQUE T.; CRUZ-MACHADO, SANSERAY DA SILVEIRA; TURATO, WALTER M.; FILGUEIRAS, LUCIANO R.; MARKUS, REGINA P.; STEINER, ALEXANDRE A. Site-Specific Reprogramming of Macrophage Responsiveness to Bacterial Lipopolysaccharide in Obesity. FRONTIERS IN IMMUNOLOGY, v. 10, JUN 28 2019. Web of Science Citations: 0.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.