Contributions of cell subsets to cytokine production during normal and impaired wound healing

Cytokine. 2015 Feb;71(2):409-12. doi: 10.1016/j.cyto.2014.09.005. Epub 2014 Oct 3.


The objective of this study was to determine the relative contributions of different cell subsets to the production of cytokines and growth factors during normal and impaired wound healing. Cells were isolated from wounds of non-diabetic and diabetic mice and separated by magnetic sorting into neutrophils/T cells/B cells (NTB cell subset), monocytes/macrophages (Mo/Mp subset) and non-leukocytic cells including keratinocyte/fibroblast/endothelial cells (KFE subset). On both per cell and total contribution bases, the Mo/Mp subset was the dominant producer of pro-inflammatory cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6 in both non-diabetic and diabetic mice and was a significant producer of vascular endothelial cell growth factor (VEGF)-A, insulin-like growth factor (IGF)-1 and transforming growth factor (TGF)-β1. The NTB subset was also a significant producer of TNF-α and IL-10 whereas the KFE subset contributed significant amounts of VEGF, IGF-1 and TGF-β1. Sustained production of pro-inflammatory cytokines and impaired production of healing-associated factors were evident in each subset in diabetic mice. These data will be useful for further experimental and modeling studies on the role of cell subsets in wound healing as well as for designing therapeutic strategies for improving healing.

Keywords: Cytokines; Diabetes; Growth factors; Wound healing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Proliferation
  • Cytokines / metabolism*
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus, Experimental / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Inflammation / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing / immunology*


  • Cytokines
  • IL1B protein, mouse
  • Interleukin-1beta
  • Interleukin-6
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • insulin-like growth factor-1, mouse
  • vascular endothelial growth factor A, mouse
  • Insulin-Like Growth Factor I