A Medical Research and Evaluation Facility (MREF) and Studies Supporting the Medical Chemical Defense Program. Evaluation of Biomarkers for Sulfur Mustard Exposure in the Euthymic Hairless Mouse Model

Abstract : The objective of this study was to investigate the pharmacologic modulation of biomarkers for evaluating therapeutics against HD. The molecular biomarkers investigated, using a ribonuclease protection assay (RPA) to determine messenger ribonucleic acid (mRNA) levels, were mediators of inflammation, including several cytokines and chemokines, tenascin, and ornithine decarboxylase. Biochemical biomarkers investigated were serum amyloid P (SAP), interleukin-6 (IL-6), and interleukin-1 alpha (IL-1alpha) using ELISAs, and activity of myeloperoxidase (MPX) using a spectrophotometric method. Other endpoints included histopathology and edema measurements. Exposure to HE) resulted in a time-dependent increase in mRNA levels of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-2 (MiP-2), macrophage inflammatory protein-1 alpha (MIP-1alpha) and interleukin- 1 beta (IL-1Beta). Exposure to HD also resulted in edema and apparent increases in the protein levels of SAP and IL-6, and in the activity of MPX. Four drug treatments, olvanil, dexamethasone, hydrocortisone, and indometbacin, were shown to modulate HD-induced inflammation.