Immune Status Assessment using mRNA gene Expression of New Biomarkers in Children with Sepsis and Septic Shock: Role of G-CSF in Improving the Outcome

Abstract

Background: Sepsis is a life- threatening organ dysfunction caused by impaired host response to infection. Objectives: To assess the immune status in children with sepsis and septic shock using mRNA gene expression of 7 biomarkers; Interleukin (IL)-1ß, Tumor necrosis factor (TNF), IL-10, Programmed death protein (PD-1) and Programmed death ligand 1(PD-L1), BID (inhibitory check point), and BCL2 (anti-apoptotic). Secondly, to study the possible influence of G-CSF on the expression of these biomarkers and outcome in septic children. Methodology: This is a case controlled prospective randomized biomarker study including 65 subjects divided into 3 groups. Group 1 comprised 24 septic patients receiving G-CSF in addition to conventional treatment for sepsis. Group 2 included 17 septic patients on conventional treatment. Group 3 control group comprised 24 infants and children matched for age and sex. Two blood samples were withdrawn from each patient at day 1 and day 8. RT-PCR analysis for mRNA gene expression of the studied biomarkers were performed. Results: Group 1 showed significant increase of PD-L1 on day 8 compared to day 1 (p= 0.019) and significant increase of BID1 on day 8 (p= 0.014) and on day 1 (p= 0.08) compared to healthy children. In group 2, IL-10 showed significant decrease on day 8 compared to day 1(p= 0.02). BID1 showed highly significant increase between both days 1 and 8 versus healthy children (p = 0.001, 0.004 respectively). BCL-2 showed significant decrease in serum levels between both days 1 and 8 versus healthy children (p = 0.04 ,0.012 respectively). Conclusion: Upregulation of the apoptotic BID1 and PD-L1 expression with downregulation of IL-10 and BcL2 expression in our septic patients suggests a feature of sepsis-related immunosuppression. G-CSF had no role on the studied biomarkers release and outcome.