Accession Number:

ADA384357

Title:

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

Descriptive Note:

Final rept. Task 95-41,

Corporate Author:

BATTELLE MEMORIAL INST COLUMBUS OH

Report Date:

2000-11-01

Pagination or Media Count:

216.0

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.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE