Inflammatory signaling pathways, such as
p38 mitogen-activated protein kinase (MAPK) play a central role in host responses to injury. In previous studies by the authors, topical
p38 MAPK inhibitors effectively attenuated inflammatory signaling in a partial-thickness scald
burn model, when applied to the
burn wound immediately after injury. However, clinically relevant full-thickness scald
burn wounds may act as a barrier to topical immune modulators, and delayed application of topical
p38 MAPK inhibitors may not be effective. In this study, the authors evaluate the efficacy of topical
p38 MAPK inhibition on full-thickness scald
burns with immediate and
delayed treatment. C57/BL6 mice received "
Sham" or 30% TBSA full-thickness scald
burn injury. After injury, the
burn wounds were treated with a topical
p38 MAPK inhibitor or vehicle. The treatment group received topical
p38 MAPK inhibitor either immediately after
burn or 4 hours (delayed) after injury. All animals were killed at 12 or 24 hours.
Burn wounds underwent histological analyses. Skin and plasma were analyzed by
enzyme-linked
immunosorbent assay or real-time quantitative polymerase chain reaction for
cytokine expression. Full-thickness scald
burns resulted from immersion in 62°C water for 25 seconds. Topical
p38 MAPK inhibitor attenuated dermal
interleukin (IL)-6, MIP-2, and IL-1β expression and plasma
IL-6 and MIP-2
cytokine expression. In addition, delayed application of topical
p38 MAPK inhibitors significantly reduced dermal and plasma
cytokine expression compared with vehicle control. Topical
p38 MAPK inhibitors remain potent in reducing full-thickness
burn wound inflammatory signaling, even when treatment is delayed by several hours postinjury. Topical application of
p38 MAPK inhibitor may be a clinically viable treatment after
burn injury.