Rux largely restores lungs in Iraq PM-exposed mice, Up-regulating regulatory T-cells (Tregs)
David Lin, Jonathan Li , B.S, Rabail Razi , M.D, Niha Qamar , M.D, Laurie Levine , A.A.S, Thomas Zimmerman , D.V.M, Sayyed A. Hamidi , M.D, M.P.H, M.B.A, Millicent Schmidt , Ph.D, Marc G. Golightly , Ph.D, Todd Rueb , B.S, Andrea Harrington , Ph.D., Merrill Garnett , D.D.S, Frank Antonawich , Ph.D, Steven McClain , M.D, Edmund Miller , Ph.D, Courtney Cox, Po Hsuan Huang & Anthony M. Szema , M.D
Background: Military personnel post-deployment to Iraq and Afghanistan have noted new-onset respiratory illness. This study’s primary objective was to further develop an animal model of Iraq Afghanistan War Lung Injury (IAW-LI) and to test a novel class of anti-injury drug called RuX.
Methods: Particulate Matter (PM) samples were obtained in Iraq then characterized by spectromicroscopy. C57BL/6 mice underwent orotracheal instillation with PM, followed by drinkable treatment with RuX. Lung histology, inspiratory capacity (FlexiVent), thymic/splenic regulatory T cell (Treg) number, and whole-lung genomics were analyzed.
Results: Tracheal instillation of Iraq PM led to lung septate thickening and lymphocytic inflammation. PM-exposed mice had suppression of thymic/splenic regulatory T-cells (Tregs). Drinking RuX after PM exposure attenuated the histologic lung injury response, improved lung inspiratory capacity, and increased Tregs. Pooled whole lung genomics suggest differences among gene expression of IL-15 among control, PM, and PM + RuX groups.
Conclusions: RuX, a ruthenium and alpha-lipoic acid complex, attenuates lung injury by improving histology and inspiratory capacity via upregulation of Tregs in Iraq PM-exposed C57BL/6. Plausible genomic effects may involve IL-15 whole lung gene expression.
KEYWORDS: Burn pits, dust, fibrosis, iraq, inflammation, lung injury, mice, particulate matter, rux
GML drug candidate RUX may assist patients exposed to burn pits!