Archives of Toxicology

, Volume 79, Issue 11, pp 660–670

Involvement of tumor necrosis factor-α in sulfur mustard-induced skin lesion; effect of topical iodine

  • Uri Wormser
  • Berta Brodsky
  • Elena Proscura
  • Julie F. Foley
  • Tinette Jones
  • Abraham Nyska
Organ Toxicity and Mechanisms

DOI: 10.1007/s00204-005-0681-5

Cite this article as:
Wormser, U., Brodsky, B., Proscura, E. et al. Arch Toxicol (2005) 79: 660. doi:10.1007/s00204-005-0681-5
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Abstract

Sulfur mustard (SM), also termed mustard gas, is a potent vesicant that elicits an inflammatory response upon exposure of the skin. Evaluation of mouse ear 3 h after SM exposure revealed acute inflammatory-cell aggregates in the vascular beds accompanied by strongly TNF-α-positive neutrophils. Eight hours after SM exposure, this phenomenon became intensified and associated with infiltration into the adjacent dermis. In ear skin topically treated with iodine, however, no inflammatory cells were observed 3 h after SM exposure; 8 h postexposure, blood vessels contained very few TNF-α-positive inflammatory cells. Since TNF-α induction was shown to be associated with reactive oxygen species production, we studied the effect of iodine on activated peritoneal mouse neutrophils. Iodine elicited a concentration-dependent reduction in the oxidative burst of activated neutrophils. Iodine also scavenged hydroxyl radicals generated by glucose oxidase in a concentration-dependent manner. The involvement of TNF-α in SM-induced skin toxicity was confirmed by reduction of 49 and 30% in ear edema following administration of 1 and 2 μg anti-TNF-α antibodies, respectively. These findings were corroborated by quantitative analysis of the histological findings showing 46% reduction in acute inflammation and no signs of subacute inflammation in the treated group, in contrast to the control group treated with SM only. Other epidermal (microblister formation, ulceration, and necrosis) and dermal (neutrophilia, hemorrhage, and necrosis) parameters also showed marked reductions in the antibodies-treated group in comparison to controls. The combination of iodine and antiTNF-α antibodies might constitute a new approach for treatment of SM-exposed individuals.

Keywords

Sulfur mustard Tumor necrosis factor-α Neutrophils Iodine Mouse-ear model 

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Uri Wormser
    • 1
  • Berta Brodsky
    • 1
  • Elena Proscura
    • 1
  • Julie F. Foley
    • 2
  • Tinette Jones
    • 2
  • Abraham Nyska
    • 2
  1. 1.Department of Pharmacology, School of Pharmacy; Faculty of Medicine, Berman Building, Institute of Life SciencesThe Hebrew University of JerusalemJerusalemIsrael
  2. 2.National Institute of Environmental Health SciencesLaboratory of Experimental Pathology, National Institutes of HealthUSA