Avaliação da resposta imune inata em pacientes adultos com sepse internados na Unidade de Cuidados Intensivos do Hospital das Clínicas da UFMG (HC/UFMG)

Abstract

Background: Sepsis is defined as an uncontrolled host response to the infectious agent, which results in a raise of the pro-inflammatory molecules and the stimulation of immune cellular response. The aim of this study was to evaluate the innate immune response in septic inpatients in an intensive care unit (ICU) of a University Hospital. Methods: This is a prospective cohort study conducted at the adult Intensive Care Unit of Hospital das Clínicas da UFMG from October 2014 to January 2018. Patients were included after the diagnosis of sepsis and monitored up to one-year after the event for survival analysis. The profile of chemokines, cytokines, pentraxin-3 e Neutrophil Extracellular Traps (NETs) contained in septic patients serum were analyzed in three different periods, being 1(D1), 3(D3) e 7(D7) after inclusion in the study. Furthermore, the chemotactic activity of the blood purified and stimulated with fMLP neutrophils was analyzed using Modified Boyden's chamber. All the molecular analysis were equally executed on samples of volunteers who self-declared as healthy. Resultados: 81 patients were included in the study, with an average of 59 (18-97) years old and predominance of feminine individuals (n=42, 52%). Most of patients came from clinical hospitalization (62%), and 52% of them were diagnosed with septic shock on the inclusion. Sixteen patients (20%) died along 28 days e 32 (40%) patients died along one year. Considering all the patients, high levels of CXCL10, CXCL8, CCL3 during the three different periods (D1, D3 e D7) were observed when analyzed comparing to healthy volunteers (p<0.001). PTX3 levels were increased on the third day after the detection of sepsis when compared to healthy individuals (p=0.02). High levels of IL-6, IFN, TNF and IL10 cytokines were detected on D1 when compared to healthy volunteers. IL6 was the only cytokine associated with septic shock and CXCL10 was the chemokines that presented significantly high levels in the patients subgroup which died along one year (p<0.001). On an average, the neutrophils chemotactic activity of patients with septic shock reduced 60% when compared to the neutrophils of healthy volunteers. Apoptosis was delayed in neuthophils of patients with sepsis when compared to healthy ones (p=0.04). DNA/NETs levels were increased in patients with sepsis when compared to healthy volunteers (p<0.001); whereas the patients with sepsis, this marker was significantly high in the subgroup of patients with septic shock (p=0.04) and in the subgroup that died along 7 days (p=0.04). Conclusions: In a group of adults with sepsis, there was an increase in inflammatory chemokines and cytokines, reduction of chemotaxis, delayed apoptosis rate and NETs increased. Changes of increase of CXCL10, IL-6 and NETs and chemotaxis reduction was statistically changed in the subgroup more seriously ill patients and with worse prognosis.