Abstract

Interleukin-12 (IL-12) is a pro-inflammatory cytokine known for its role in immunity, and previous studies have shown that IL-12 provides mitigation of radiation injury. In this study, we utilize a multimodal microscopy system equipped with second harmonic generation (SHG) and fluorescence lifetime imaging microscopy (FLIM) to examine the effect of IL-12 on collagen structure and cellular metabolic activity in vivo during skin wound healing. This preliminary study illustrates the highly dynamic and heterogeneous in vivo microenvironment of the wounded skin. In addition, results suggest that IL-12 triggers a significantly more rapid and greater cellular metabolic response in the wounded animals. These results can elucidate insights into the response mechanism of IL-12 in both wound healing and acute radiation syndrome.

Highlights

  • Interleukin-12 (IL-12) is a pro-inflammatory cytokine primarily produced by monocytes, macrophages, and dendritic cells that is known to be involved in the development of cellmediated immunity, and to form a link between innate resistance and adaptive immunity [1, 2]

  • second harmonic generation (SHG) was utilized to track the progress of wound healing and to evaluate the collagen structure around the wound bed within the first 100 μm depth of the dermal skin layer

  • We demonstrated in vivo longitudinal SHG and fluorescence lifetime imaging microscopy (FLIM) imaging and tracking of wound healing post administration of rMuIL-12

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Summary

Introduction

Interleukin-12 (IL-12) is a pro-inflammatory cytokine primarily produced by monocytes, macrophages, and dendritic cells that is known to be involved in the development of cellmediated immunity, and to form a link between innate resistance and adaptive immunity [1, 2]. IFN-γ can interact with nearby cells through paracrine signaling to ensure the continuous presence of essential cytokines and immune cells [3]. Injury triggers a complex and organized cascade of cellular and biochemical events that eventually lead to healed skin. This healed skin is not as structurally and functionally strong as non-wounded skin [5, 6]. The inflammatory stage is an essential phase of healing, during which cytokines, growth factors, and immune cells including macrophage and dendritic cells are released and activated [1, 3]

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