Arginase‐1 Expression in Human Peripheral Blood is Associated With an Impaired Ability to Support Lymphocyte Proliferation Following Ischemic Brain Injury

Abstract

Ischemic brain injury produces an immediate inflammatory response followed by systemic immune suppression. This immunosuppressed state, characterized by lymphopenia and impaired macrophage function, facilitates further tissue damage and is associated with impaired recovery. The primary factors modulating post‐ischemic immune suppression have yet to be realized. Arginase‐1 (ARG1) is an immunomodulatory ureohydrolase with immunosuppressive properties. Data produced by our laboratory have shown that ARG1 is strongly induced in peripheral blood following ischemic stroke in humans. Thus, we tested the hypothesis that ARG1 plays a critical role in propagating the immunosuppressed state following ischemic neurological insult. To address this hypothesis, total RNA and serum was extracted from peripheral blood samples obtained from 9 male human subjects within 24 hours of transient ischemic attack or ischemic stroke. qRT‐PCR was performed to quantify peripheral blood ARG1 expression levels, and a CSFE‐based proliferation assay was used to evaluate the capacity of post‐ischemic serum to support proliferation of the Jurkat human T‐cell line in‐vitro. Peripheral blood ARG1 expression was negatively associated with Jurkat proliferation, however this correlation failed to reach statistical significance at a confidence interval of 0.95 (Spearman correlation: r=‐0.64, p=0.06). Based on the relative strength of association observed in this small clinical sample, we believe that the role of ARG1 as a post‐ischemic immune modulator warrants further investigation, as ARG1 may represent a critical factor driving immune suppression following ischemic brain injury.