Upregulation of interleukin-13 and its receptor in a murine model of bleomycin-induced scleroderma

Int Arch Allergy Immunol. 2004 Dec;135(4):348-56. doi: 10.1159/000082331. Epub 2004 Nov 24.


Background: Interleukin-13 (IL-13) has been implicated in the pathogenesis of fibrotic conditions. Previously, a murine model for scleroderma has been established by repeated local injections of bleomycin. This animal model enabled us to study local expression and production of IL-13 in skin lesions during disease progression.

Methods: Dermal sclerosis (DSc) was induced by repeated subcutaneous injections of bleomycin (1 mg/ml) in C3H/HeJ mice. IL-13 and IL-4 expressions were examined by RT-PCR, ELISA and immunohistochemistry.

Results: RT-PCR showed that both IL-4 and IL-13 mRNA levels in skin lesions were increased and peaked after 4 weeks of bleomycin treatment. Quantification by densitometry revealed up to 4.2- and 1.9-fold increases, respectively. Immunohistochemical localization showed in skin lesions expression of IL-13 on infiltrating inflammatory cells, including mononuclear cells and possibly mast cells, increased with DSc progression. IL-13 protein production was also significantly increased. In skin lesions, IL-13 receptor (IL-13R) alpha2 expression was augmented mainly in the infiltrating mononuclear cells after 4 weeks of bleomycin exposure. IL-13Ralpha2, but not IL-13Ralpha1, mRNA was upregulated in the whole skin after 4 weeks. On the contrary, mRNA expression of IL-13Ralpha1 and IL- 13Ralpha2 was significantly altered in the cultured fibroblasts derived from bleomycin-treated skin.

Conclusion: These data demonstrate that in skin lesions levels of IL-13 as well as its receptor increase in parallel with DSc progression, suggesting that IL-13 promotes the progression of cutaneous fibrosis/sclerosis in the murine model of bleomycin-induced scleroderma.

MeSH terms

  • Animals
  • Biopsy, Needle
  • Bleomycin
  • Disease Models, Animal
  • Female
  • Immunohistochemistry
  • Interleukin-13 / biosynthesis
  • Interleukin-13 / genetics
  • Interleukin-13 / immunology*
  • Interleukin-13 Receptor alpha1 Subunit
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology*
  • Mice
  • Mice, Inbred C3H
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptors, Interleukin / biosynthesis
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / immunology*
  • Receptors, Interleukin-13
  • Reverse Transcriptase Polymerase Chain Reaction
  • Scleroderma, Systemic / chemically induced
  • Scleroderma, Systemic / immunology*
  • Scleroderma, Systemic / pathology
  • Skin Diseases / chemically induced
  • Skin Diseases / immunology*
  • Skin Diseases / pathology
  • Specific Pathogen-Free Organisms
  • Statistics, Nonparametric
  • Up-Regulation / immunology


  • Il13ra1 protein, mouse
  • Interleukin-13
  • Interleukin-13 Receptor alpha1 Subunit
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-13
  • Bleomycin
  • Interleukin-4