HMGB1 and inflammmatory cytokines in experimental acute lung injury (ALI)

• Grant number: 11/15144-2
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2011
• End date: December 31, 2013
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Cilmery Suemi Kurokawa
• Grantee: Cilmery Suemi Kurokawa
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Ana Paula Mena Lousada ; João Pessoa Araújo Junior ; José Roberto Fioretto ; Susiane de Oliveira Klefens

Abstract

Acute lung injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) are characterized by lung inflammation that leads disruption of alveolar-capillary membrane with development of interstitial / alveolar edema, decreased of lung compliance, pulmonary hypertension, imbalance of ventilation / perfusion ratio and severe hypoxemia with refractory to oxygen administration. Despite improvement in supportive care and knowledge about physiopathology of ALI, mortality rate remains high, between 26 and 35%, driving the studies on ALI. Considering these facts, this study will evaluate the levels of IL-8, TNF-alpha and HMGB1 in bronchoalveolar lavage and tissue and expression in lung tissue of TLR2 and 4 in animals with two grade of lung lesion. For this, 45 rabbits of 2.5 kg will be divided in three groups: severe lesions (S), animals with ALI and PaO2 <100 mmHg; Moderate/mild injury group (M), animals with ALI and PaO2 between 300 and 200 mmHg and Control Group (C), rabbits without ALI. All animals will be ventilated with protective mechanical ventilation (PMV) and ALI will be induced by tracheal infusion of warm saline (30 ml / kg, 38oC) in lung. The oxygenation indices are obtained by blood gas analysis to compose the group with moderate and severe ALI. After induction of ALI and ventilation, the animals will be euthanized, collected the bronchoalveolar lavage and fragments of lung tissue to determine the concentration of IL-8, TNF-alpha, TLR-2 and 4 mRNA. HMGB-1 and neutrophil count will be determined only in bronchoalveolar lavage. The static lung compliance and mean of airway pressure will associate with cytokines, receptors, HMGB1 and neutrophil count. (AU)

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)

C.S. KUROKAWA; J.P. ARAÚJO JÚNIOR; R.B. PIRES; M.F. CARPI; M.A. MORAES; L.T.L. MEDEIROS; J.R. FIORETTO. [HMGB1 e citocinas inflamatórias em lesão pulmonar aguda experimental induzida em coelhos]. Arquivo Brasileiro de Medicina Veterinária e Zootecnia, v. 72, n. 4, p. 1329-1338, 2020-08-14. (11/15144-2)