Efeito do imiquimode na cicatrização de queimaduras em ratos

Abstract

Burns can result in substantial morbidity because of fibroblastic hyperproliferation and contracture. Imiquimod is a immunomodifier -TLR-7 agonist used in viral diseases and in neoplastic conditions like actinic keratosis, melanoma, and non-melanoma skin cancer. It acts by promoting endogenous cytokines known to suppress fibroblast proliferation. A new recent use is in treating keloids and hypertrophic scars to reduce scarring. No study of the effect of imiquimod on cutaneous burns has been performed. This study examined burn healing in the presence of topical imiquimod by evaluation of wound appearance, computer-aided image analysis, and histology in a rat model. Standardized partial-thickness burns were produced on the dorsum of thirty-two Wistar rats. Right-sided wounds received therapy with isotonic saline (sham). Left-sided wounds were treated with imiquimod cream at 5% (IMQ). This was repeated 3 times/week after injury. Euthanasia was performed at 4th, 7th, 14th and 21st Postburn days (PBD). Wounds were harvested for histological analysis. Evaluation of wound appearance was performed using clinical assessment scale (CAS) and a visual analogue scale (VAS). Scars area and perimeter were measured using digital planimetry to assess wound edge migration by Gilman’s modified Equation. Inflammation type and intensity was graded by histological scale. Collagen type was identified by picrosirius-polarization and morphometric analysis was performed. VAS scores showed discretally improved appearance in the imiquimod-treated wounds versus the saline-treated control at PBD21 (P=0.0491). There was no difference in CAS scores. Wound edge migration was significantly slowest in imiquimod-treated wounds (p<0.05). Histological evidence of partial thickness dermal injury with sparing of dermal appendage epithelial cells was seen in all wounds. Histologic characteristics of gradually diminished injured area between groups were similar except in imiquimod-treated wounds at PBD14 (p<0.05). Inflamattory state was bigger in imiquimod-treated wounds at PBD7 and PBD21 (p<0.005). At PBD7 there was no chronic-type of inflammatory reaction in imiquimod-treated group, although in saline-treated group chronic plus sub-acute type was present in 87.5% (p<0.005). At PBD21 68.75% of imiquimod-treated group showed acute plus subacute inflammatory state, and saline-treated group displayed chronic-type in 56.25% of the wounds. The total amount of collagen increased in both groups throughout all time points. Morphometry showed an inversed ratio type I to type III collagen. Ratios of type I collagen to type III collagen was much lower in imiquimod-treated wounds at PBD4 and PBD21. Topical treatment with Imiquimod 5% cream for partial-thickness burn wounds 3 times/week courses do not improve clinical appearance and scarring during late healing. There is no difference in histology during the short-term healing process. Computer-aided image proccessing was efficient to evaluate burned-wound healing. Wound healing and fibrosis was impaired in imiquimod- treated wound group.