Kolliphor EL Alters IgE-Mediated Immune Functions 2266473

Abstract Introduction Food allergies (FA) are becoming increasingly prevalent worldwide, affecting more than 220 million people globally. Anaphylaxis is the most rapid and severe allergic reaction resulting in a rapid drop in blood pressure, constriction of airways, hives and swelling, gastrointestinal symptoms, and can be deadly. IgE-mediated anaphylaxis occurs when mast cells (MCs) with IgE bound to its high affinity receptor become crosslinked by allergen, leading to degranulation and the release of mediators such as histamine and tryptase, causing allergic symptoms. While food allergens are the most well-known trigger, drug-induced anaphylaxis is often linked to the solubilizing agents in pharmaceutical formulations; however, this is poorly understood. Kolliphor EL (KE) also known as PEG-35 castor oil, is a commonly used non-ionic surfactant and drug solubilizer. KE has been reported to trigger MC activation leading to hypersensitivity and anaphylactic reactions, although it is unclear if these are IgE dependent or not. Methods IgE sensitized bone marrow derived mast cells (BMMCs) from wild-type C57B/6 mice were pre-treated with KE for 1 hour before antigen IgE crosslinking. Beta hexosaminidase was measured using an enzymatic reaction 30 minutes after crosslinking and IL-13 was measured by ELISA 16 hours after crosslinking. For in vivo experiments C57B/6 mice were injected with DNP specific IgE and KE. The next day, mice received another dose of KE 1 hour before DNP induced anaphylaxis. Results Surprisingly, we demonstrate that KE decreased IgE-mediated degranulation and IL-13 production in a dose-dependent manner in vitro. In vivo, mice treated with KE were protected against IgE-mediated passive systemic anaphylaxis. Conclusion Collectively, these findings suggest that KE modifies immune responses that require further investigation. This research aims to determine whether KE’s immune effects can be beneficial for treatment of anaphylaxis or whether it should be more carefully restricted in clinical formulations. Funding Source N/A Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)