Cytokine and chemokine dynamics differ between rats and mice after collagen implantation

J Tissue Eng Regen Med. Sep-Oct 2007;1(5):398-405. doi: 10.1002/term.50.


Implanted scaffold materials induce an inflammatory reaction known as the 'foreign body reaction' (FBR). We hypothesized that the observed difference in FBR between rats and mice correlate with different expression dynamics of cytokines and chemokines, which are key orchestrators of the FBR. After implantation of hexamethylene diisocyanate cross-linked dermal sheep collagen, the overall gene expression pattern of IL-1, IL-6, IL-10, TNFalpha, CXCL1/KC, CXCL2/MIP2 and CCL2/MCP1 was roughly similar for the two species. During the onset of the FBR these genes were maximally expressed in rats and mice, after which the expression decreased to basal levels. The expression of CCL3/MIP1 alpha had a similar course, yet it increased after the progression phase of the FBR in both species. The expression of cytokines and chemokines in sham-operated animals was low throughout, showing that the implanted material by itself exerted the changes in gene expression of the invading cells. During the progression, genes encoding the PMN attractants CXCL1/KC and CXCL2/MIP2 were more highly expressed in mice than in rats, which would explain the prolonged presence of PMNs in mice during the FBR. Additionally, the strong induction of IFN gamma in rats coincided with a higher phagocytotic activity by macrophages. Throughout the FBR, the expression of TGFbeta was constitutive and high in both species, but increased in mice during the progression phase. This could explain the extensive stroma formation during the murine FBR. Unexpectedly, the stronger expression of TNFalpha and CCL3/MIP1 alpha in mice, did not result in high macrophage attraction or phagocytosis of the implanted collagen disks.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Chemokines / genetics
  • Chemokines / metabolism*
  • Chemokines / pharmacology
  • Collagen / metabolism*
  • Cross-Linking Reagents / chemistry
  • Cyanates / chemistry
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Cytokines / pharmacology
  • Foreign-Body Reaction / genetics
  • Foreign-Body Reaction / metabolism
  • Foreign-Body Reaction / pathology
  • Gene Expression
  • Giant Cells / physiology
  • Immunohistochemistry
  • Implants, Experimental*
  • Interferon-gamma / biosynthesis
  • Isocyanates
  • Macrophages / physiology
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / immunology
  • Phagocytosis
  • Rats
  • Rats, Inbred Strains
  • Sheep
  • Skin
  • Species Specificity
  • Transforming Growth Factor beta / metabolism


  • Chemokines
  • Cross-Linking Reagents
  • Cyanates
  • Cytokines
  • Isocyanates
  • Transforming Growth Factor beta
  • 1,6-hexamethylene diisocyanate
  • Interferon-gamma
  • Collagen