Erythropoietin reduces the degree of arthritis caused by type II collagen in the mouse

Salvatore Cuzzocrea, Emanuela Mazzon, Rosanna D. Paola, Tiziana Genovese, N. S A Patel, Domenico Britti, Massimo De Majo, Achille P. Caputi, Christoph Thiemermann

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Abstract

Objective. Erythropoietin (EPO) is a potent stimulator of erythroid progenitor cells, and its expression is enhanced by hypoxia. The aim of this study was to investigate the effect of EPO on collagen-induced arthritis (CIA) in the mouse. Methods. CIA was induced by intradermal injection of bovine type II collagen (CII) and Freund's complete adjuvant. Starting on day 25, some of the mice with CIA received daily subcutaneous injections of EPO (1,000 units/kg). Two other groups of mice received sham treatment alone or sham treatment followed by EPO treatment, respectively. Arthritis was assessed clinically, radiologically, and histologically. Cytokine and chemokine levels were measured, and neutrophil infiltration into inflamed joints was quantitated. Immunohistochemistry studies were performed to measure protein nitrosylation. Chondrocyte apoptosis was assessed by TUNEL assay. Results. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hind paws. The incidence of CIA was 100% by day 27 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period, with radiographic evaluation revealing focal resorption of bone. Histopathologic features of CIA included erosion of the cartilage at the joint margins. Treatment with EPO starting at the onset of arthritis (day 25) ameliorated the clinical signs on days 26-35 and improved histologic status in the joints and paws. The degree of oxidative and nitrosative damage was significantly reduced in EPO-treated mice as indicated by decreased nitrotyrosine formation and poly(ADP-ribose) polymerase activation. Plasma levels of the proinflammatory cytokine tumor necrosis factor α were also significantly reduced by EPO treatment. In addition, EPO reduced the levels of apoptosis in chondrocytes in articular cartilage, as indicated by decreased TUNEL staining. Conclusion. These findings demonstrate that EPO exerts an antiinflammatory effect during chronic inflammation and is able to ameliorate the tissue damage associated with CIA.

Original languageEnglish
Pages (from-to)940-950
Number of pages11
JournalArthritis and Rheumatism
Volume52
Issue number3
DOIs
Publication statusPublished - Mar 2005

Fingerprint

Collagen Type II
Experimental Arthritis
Erythropoietin
Arthritis
Joints
In Situ Nick-End Labeling
Chondrocytes
Placebos
Apoptosis
Cytokines
Intradermal Injections
Erythroid Precursor Cells
Poly(ADP-ribose) Polymerases
Freund's Adjuvant
Neutrophil Infiltration
Articular Cartilage
Subcutaneous Injections
Erythema
Bone Resorption
Chemokines

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Cuzzocrea, S., Mazzon, E., Paola, R. D., Genovese, T., Patel, N. S. A., Britti, D., ... Thiemermann, C. (2005). Erythropoietin reduces the degree of arthritis caused by type II collagen in the mouse. Arthritis and Rheumatism, 52(3), 940-950. https://doi.org/10.1002/art.20875

Erythropoietin reduces the degree of arthritis caused by type II collagen in the mouse. / Cuzzocrea, Salvatore; Mazzon, Emanuela; Paola, Rosanna D.; Genovese, Tiziana; Patel, N. S A; Britti, Domenico; De Majo, Massimo; Caputi, Achille P.; Thiemermann, Christoph.

In: Arthritis and Rheumatism, Vol. 52, No. 3, 03.2005, p. 940-950.

Research output: Contribution to journalArticle

Cuzzocrea, S, Mazzon, E, Paola, RD, Genovese, T, Patel, NSA, Britti, D, De Majo, M, Caputi, AP & Thiemermann, C 2005, 'Erythropoietin reduces the degree of arthritis caused by type II collagen in the mouse', Arthritis and Rheumatism, vol. 52, no. 3, pp. 940-950. https://doi.org/10.1002/art.20875
Cuzzocrea, Salvatore ; Mazzon, Emanuela ; Paola, Rosanna D. ; Genovese, Tiziana ; Patel, N. S A ; Britti, Domenico ; De Majo, Massimo ; Caputi, Achille P. ; Thiemermann, Christoph. / Erythropoietin reduces the degree of arthritis caused by type II collagen in the mouse. In: Arthritis and Rheumatism. 2005 ; Vol. 52, No. 3. pp. 940-950.
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AU - Patel, N. S A

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