Selection of non-steroidal anti-inflammatory drug and treatment regimen for sulfur mustard-induced cutaneous lesions

Abstract

The inflammatory process plays an important role in sulfur mustard (HD) injury and HD pathogenesis, suggesting that anti-inflammatory treatments applied as soon as possible following HD injury may reduce tissue damage and accelerate healing. This study used the HD dermal weanling swine model to investigate the efficacy of two non-steroidal anti-inflammatory drugs, capsaicin and diclofenac, when applied in combination with the steroid, clobetasol. The therapeutic regimen was also investigated with respect to initiation of treatment post-exposure, frequency and duration. Yorkshire-cross pigs were randomly assigned to experimental groups, corresponding to all combinations of treatment (capsaicin with clobetasol or diclofenac with clobetasol), onset time (1, 2 or 4 h post-exposure), treatment duration (1, 3 or 5 days) and frequency of applications (2, 3 or 4 per day). For each animal, two sites on the ventral abdomen were exposed to 400 μL of neat HD for 8 min to achieve superficial dermal (SD) lesions and two sites were exposed to 400 μL neat HD for 30 min to achieve deep dermal (DD) lesions. Each treatment regimen was tested against a SD and a DD injury. Untreated SD and DD lesion sites served as within-animal controls. Assessments, up to one week post-challenge, included digital photographs, clinical assessments (lesion size measurements and modified Draize scoring), transepidermal water loss (TEWL), reflectance colorimetry and histopathologic evaluations that included an estimate for depth of injury and wound healing parameters. Diclofenac plus clobetasol treatment resulted in significant reductions in lesion contracture and modified Draize scores, increased barrier function (decreased TEWL), and increased healing as determined by histopathology for both SD and DD injury when compared with untreated sites and sites treated with capsaicin plus clobetasol. An increased duration of treatment from 1 to 5 days was most commonly associated with decreased clinical assessment and histopathological severity scores. Therefore, a combination of diclofenac and clobetasol application, when administered for at least five days, shows promise in ameliorating HD-induced lesions.

• Capsaicin
• chemical agent
• clobetasol
• dermal
• diclofenac
• sulfur mustard
• swine
• therapy

Acknowledgements

The authors would like to thank Jennifer Solt, William Hart, Jerrika Rhone, and Nathan Gargas for their technical assistance, N. Niemuth for statistical analysis, M. A. Buccellato for histopathology support, and Dr P. Sabourin for report editing on this study.

Declaration of interest

This work was conducted under DTRA/CBMS/MRMC Contract W81XWH-05-D-0001, Task Order 0010 with funding support through an Interagency Agreement (IAA) between the U.S. Army Medical Research Institute of Chemical Defense (USAMRICD) and National Institutes of Health, National Institute of Allergies and Infectious Disease (NIAID), IAA Number Y1-AI-6177-02. The views, opinions, and/or findings contained in this report are those of the authors and should not be construed as an official Department of the Army position, policy, or decision unless so designated by other documentation. The experimental protocol was approved by the Animal Care and Use Committee at Battelle Memorial Institute and the US Army Medical Research and Materiel Command’s Animal Care and Use Review Office. All procedures were conducted in accordance with the principles stated in the Guide for the Care and Use of Laboratory Animals (National Research Council, 1996), and the Animal Welfare Act of 1966 (P.L. 89–544), as amended. The authors have no conflicts of interest that would affect the interpretation or conclusions of this study.