Objectives/Goals: Our goal is to improve health outcomes for sepsis survivors experiencing immune-paralysis. We propose a functional diagnostic tool to identify at-risk patients and a novel therapeutic called interleukin-7 to boost the patient’s T-cell-mediated immunity against infection. Methods/Study Population: This multi-center research study recruits healthy adult volunteers and adult septic patients in the intensive care unit to consent to giving blood draws. Blood draws containing immune cells are assessed for functionality through our diagnostic tool. Interleukin-7, a therapeutic candidate to improve immune cell activity, is assessed by flow cytometry, ELISA, and bulk RNA sequencing. Results/Anticipated Results: Using IL-7 during T-cell stimulation in the ELISpot assay increased the number of T-cells producing protective effector protein IFNgamma. Statistical analysis was performed using Brown-Forsythe ANOVA test with Dunnett’s T3 multiple comparisons test with a P-value<0.001. Flow cytometry confirms IL-7 treatment increased the frequency of T-cells to produce IFNgamma and preferentially impacts memory T-cells in sepsis patients. Bulk mRNA sequencing demonstrated increased differentially expressed mRNA transcripts FDR<.001 related to cell survival and T-cell-mediated effector molecules with IL-7-treated cells. IL-7 improved effector protein production was confirmed by a multiplex assay. Discussion/Significance of Impact: There are no diagnostic tools to identify immunocompromised patients or therapies to reverse the immune suppression. Our ELISpot diagnostic tool identifies at-risk immune-impaired patients. Furthermore, our results demonstrate interleukin-7 as a potential therapeutic to improve immune activity.
Kim et al. (Wed,) studied this question.