Tewari-Singh Lab Investigating the Immune Mechanism of Mustard Gas Toxicity

November 23, 2020

IIT-affiliated faculty member Neera Tewari-Singh recently began work on a Department of Defense Tier 1 Discovery award focused on identifying a novel immune mechanism of mustard gas (sulfur mustard; SM) toxicity, which could also be applicable to other chemical exposures in Gulf War Illness (GWI). The grant, “Mast cells in sulfur mustard exposure: novel targets for modulation to develop therapies against the long-term health effects in Gulf War Veterans,” is funded through the Gulf War Illness Research Program in the Department of Defense Congressionally Directed Medical Research Programs.  

It is reported that during the Gulf War (1990-1991) U.S. troops could have been exposed to a number of chemicals including the low levels of chemical warfare agents (CWAs) like SM. Studies in the U.S. and other locations have dependably established that approximately 25-32% of Gulf War veterans suffer from a disorder with variable symptoms including fatigue, headaches, cognitive dysfunction, musculoskeletal pain, and respiratory, gastrointestinal and dermatologic complaints. These symptoms of GWI relate closely to the long-term consequences observed with SM exposure. Mast cells are well known to contribute to allergic inflammatory diseases, but also have wide ranging effects on many physiological systems that are affected in GWI including pulmonary, dermal, gastrointestinal and nervous systems when activated (e.g. degranulation). Importantly, a role for mast cells has been suggested in the mechanism of vesicating chemical agents like SM-induced inflammatory response and tissue damage.

Tewari-Singh, under this project, will embark on understanding the role of mast cell-induced immune responses in vesicant inhalation and skin exposures using nitrogen mustard [NM; bis(2-chloroethyl) methylamine] as a surrogate for SM. Tewari-Singh and her team are conducting cell culture studies to elucidate mast cell-induced immune responses following mustard vesicating agent exposure. Further, in vivo studies in mast cell and wild-type mice are also planned, to confirm the role for mast cells in NM-induced skin and lung toxicity as well as inflammation.

For over a decade, Tewari-Singh has worked with the National Institutes of Health’s Countermeasures Against Chemical Threats (CounterACT) program, to understand the mechanisms related to the inflammation/injuries from exposure to chemical threats including vesicating agents. Her goal is to further use this information to identify targeted therapies.

“I am extremely excited about this project,” said Tewari-Singh, an assistant professor in the Department of Pharmacology and Toxicology, “because the proposed studies will have a strong potential to aid in understanding the mechanism of the inflammatory process and immune response following low exposures to alkylating warfare agent SM. The identification of applicable markers for therapeutic approaches will have a strong translational impact to potentially develop targeted treatments against chronic SM exposure. These treatments will be highly valuable in GWI, and for future veterans as well as vulnerable civilian populations, who are at risk to be exposed to similar chemical agents.”