150. The Impact of body-only proton radiation on immune-CNS communication

Abstract

Hematopoietic stem cell transplant (HSCT) is an established treatment for many hematological disorders including lymphomas and leukemias. Although the prognosis after HSCT has historically been poor, associated with high mortality rates, advances in treatment have led to increases in long-term survival and, consequently, an increased risk for neuropsychological dysfunction. Roughly 40% of all allogeneic HSCTs performed in 2006–2010 involved total body irradiation (TBI) conditioning. Previously, we reported that many TBI-induced changes in splenic phagocytic populations were mitigated by chlorisondamine (CHL), a non-selective nicotinic blocker that crosses the blood–brain barrier. In this study, we characterized the effects of body-only proton irradiation (excluding brain) and CHL on the response to a bacterial challenge in 8- to 10-week-old female C57BL/6 mice. Mice were given CHL (1 mg/kg, i.p.) and irradiated (0 or 3 Gy) 60–90 min later. Ten days post-irradiation, mice were inoculated with 5e7 CFU of Escherichia coli (i.p.) and euthanized 90–120 min later. We characterized blood and splenic leukocyte population distributions (flow cytometry and hematology), cytokine levels (multiplexed cytokine analysis) and oxidative burst capacity. Radiation decreased virtually all splenic leukocyte counts while increasing oxidative burst capacity. In the blood, radiation decreased lymphocytes but increased innate subsets. Sympathetic blockade did not counter most of these radiation effects. This suggests that the disruptive effect of TBI on brain–immune communication is dependent on direct exposure to the brain.