Tempering lethal irradiation induced pro-inflammatory responses in lethally irradiated animals by G-003M: A Potential Radio-modifying approach

Abstract

Abstract Repair of lethal radiation associated hemopoietic / gastrointestinal syndrome within an amicable post irradiation time is paramount for radio recovery. In this context, our previous studies have demonstrated the significance of CD14+high macrophages are critical for the management of radiation induced injuries. In this study we report that one of our radioprotective formulations (G-003M) potentially inhibited lethal radiation and/or LPS induced NO and Th1 effector cytokines in the exposed macrophages and lethally irradiated animals indicating its M1 dim polarizing capacity. Preconditioning of mice with G-003M before exposure to lethal irradiation (LR) inhibited Th1 effector cytokines in serum, lung, small intestine, and splenic tissue confirming its anti-inflammatory potential in these models. Of note, G-003M mediated M2 polarization of LPS primed iNOS+ M1 effector macrophages indicating its potential to temper plasticity of inflammatory macrophages that are potentially involved in sensitization of lethally irradiated host highlighting its adjunct role in mitigating radiation syndromes and affording radioprotection. G-003M potentially re-programs lethally irradiated macrophages, explicitly demonstrating that re-programming of inflammatory macrophages and / or response by G-003M may contribute to the tissue homeostasis radio recovery