IL‐5‐overexpressing mice exhibit eosinophilia and altered wound healing through mechanisms involving prolonged inflammation

Abstract

Leucocytes are essential in healing wounds and are predominantly involved in the inflammatory and granulation stages of wound repair. Eosinophils are granulocytic leucocytes and are specifically regulated by interleukin-5 (IL-5), a cytokine produced by T helper 2 (Th2) cells. To characterize more clearly the role of the IL-5 and eosinophils in the wound healing process, IL-5-overexpressing and IL-5-deficient mice were used as models of eosinophilia and eosinophil depletion, respectively. Our results reveal a significantly altered inflammatory response between IL-5-overexpressing and IL-5 knockout mice post-wounding. Healing was significantly delayed in IL-5-overexpressing mice with wounds gaping wider and exhibiting impaired re-epithelialization. A delay in collagen deposition was observed suggesting a direct effect on matrix synthesis. A significant increase in inflammatory cell infiltration, particularly eosinophils and CD4 + cells, one of the main cell types which secrete IL-5, was observed in IL-5-overexpressing mice wounds suggesting that one of the main roles of IL-5 in wound repair may be to promote the infiltration of eosinophils into healing wounds. Healing is delayed in IL-5-overexpressing mice and this corresponds to significantly increased levels of eosinophils and CD4 + cells within the wound site that may contribute to and exacerbate the inflammatory response, resulting in detrimental wound repair.

Analysis of the Molecular Biologic Milieu of the Vitreous in Proliferative Vitreoretinopathy

“…Interleukin 5 is associated with prolonged inflammation and aberrant wound healing in murine models. 18 Hollborn et al 19 IL-15 messenger RNA expression in retinal pigment epithelial cells after challenge with proinflammatory molecules, indicating that the enrichment that we detected in our study is a logical consequence of retinal pigment epithelial stimulation. Additionally, IL-15 has been implicated in the retinopathy of prematurity, suggesting a role in retinal pathology.…”

Neotenic phenomenon in gene expression in the skin of Foxn1- deficient (nude) mice - a projection for regenerative skin wound healing

“…It should be noted that these two cytokines were shown to influence tissue remodeling (e.g., via regulation of matrix metalloproteinases (Mmps) and fibronectin expression). Additionally, proinflamatory cytokines Il-18 and Il-5 [34, 35], which are normally rapidly translated in response to injury, are already up-regulated in un-injured skin of nude and E14 (Table 1). Slightly up-regulated levels of pro-inflammatory cytokines can be beneficial for regenerative resolving of wound healing process, as cytokines attract and stimulate cells (i.e., dermal fibroblasts) at the place of injury.…”

Host protective roles of type 2 immunity: Parasite killing and tissue repair, flip sides of the same coin

“…In fact the converse has been shown, with IL-5-transgenic mice displaying a delay in incisional wound repair [137]. The repair-related properties of eosinophils are so diverse and likely implicate remodeling of extracellular matrix, which involves both breakdown and synthesis.…”