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Combination leflunomide and methotrexate impedes the recovery of liver fibrosis, partly through inhibition of myeloid cell admittance

  • Authors:
    • Mengxin Lin
    • Ruyi Guo
    • Zhijun Su
    • Shaopeng Ke
    • Dawu Zeng
  • View Affiliations / Copyright

    Affiliations: Department of Infectious Disease, The First Hospital of Quanzhou City, Quanzhou, Fujian 362000, P.R. China
    Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1622-1628
    |
    Published online on: January 4, 2019
       https://doi.org/10.3892/mmr.2019.9821
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Abstract

The process of liver fibrosis is reversible and involves a recovery phase. In the present study, the potential side effects of combination leflunomide and methotrexate (LEF+MTX), a conventional rheumatoid arthritis therapy used in the resolution of liver fibrosis, was investigated. In a carbon tetrachloride‑induced liver fibrosis model, the results of hepatic pathology demonstrated that the LEF+MTX combination delayed the recovery of fibrosis, although the activation of hepatic stellate cells in vitro was inhibited. A total of four liver fibrosis‑associated indicators, hyaluronic acid, laminin, procollagen type III and collagen IV, maintained high levels in the serum of LEF+MTX‑treated mice, while detection of bone marrow‑driven monocytes in the blood by flow cytometry indicated that they were significantly decreased. Notably, the results of immunofluorescence staining of hepatic myeloid cells and detection of vascular growth factor A (VEGF‑A) in blood and liver suggested that the reduced degeneration of collagen in liver sinusoids was associated with decreased myeloid cell adhesion and the downregulation of VEGF‑A in the liver. The present results suggested that in certain cases, treatment with LEF+MTX may impede the recovery of hepatic fibrosis‑associated diseases in mice.
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1 

Patten DA and Shetty S: Chronic liver disease: Scavenger hunt for novel therapies. Lancet. 391:104–105. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Tsuchida T and Friedman SL: Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol. 14:397–411. 2017. View Article : Google Scholar : PubMed/NCBI

3 

Pellicoro A, Ramachandran P, Iredale JP and Fallowfield JA: Liver fibrosis and repair: Immune regulation of wound healing in a solid organ. Nat Rev Immunol. 14:181–194. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Janssen NM and Genta MS: The effects of immunosuppressive and anti-inflammatory medications on fertility, pregnancy, and lactation. Arch Intern Med. 160:610–619. 2000. View Article : Google Scholar : PubMed/NCBI

5 

Dougados M, Emery P, Lemmel EM, Zerbini CA, Brin S and van Riel P: When a DMARD fails, should patients switch to sulfasalazine or add sulfasalazine to continuing leflunomide? Ann Rheum Dis. 64:44–51. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Wessels JA, Huizinga TW and Guchelaar HJ: Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis. Rheumatology (Oxford). 47:249–255. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Rozman B: Clinical pharmacokinetics of leflunomide. Clin Pharmacokinet. 41:421–430. 2002. View Article : Google Scholar : PubMed/NCBI

8 

Lee SW, Park HJ, Kim BK, Han KH, Lee SK, Kim SU and Park YB: Leflunomide increases the risk of silent liver fibrosis in patients with rheumatoid arthritis receiving methotrexate. Arthritis Res Ther. 14:R2322012. View Article : Google Scholar : PubMed/NCBI

9 

Ferri C, Sebastiani M, Antonelli A, Colaci M, Manfredi A and Giuggioli D: Current treatment of hepatitis C-associated rheumatic diseases. Arthritis Res Ther. 14:2152012. View Article : Google Scholar : PubMed/NCBI

10 

Kantari-Mimoun C, Castells M, Klose R, Meinecke AK, Lemberger UJ, Rautou PE, Pinot-Roussel H, Badoual C, Schrödter K, Österreicher CH, et al: Resolution of liver fibrosis requires myeloid cell-driven sinusoidal angiogenesis. Hepatology. 61:2042–2055. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Duffield JS, Forbes SJ, Constandinou CM, Clay S, Partolina M, Vuthoori S, Wu S, Lang R and Iredale JP: Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest. 115:56–65. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Kilkenny C, Browne W, Cuthill IC, Emerson M and Altman DG; National Centre for the Replacement, Refinement and Reduction of Amimals in Research, : Animal research: Reporting in vivo experiments-the ARRIVE guidelines. J Cereb Blood Flow Metab. 31:991–993. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Fontana RJ, Dienstag JL, Bonkovsky HL, Sterling RK, Naishadham D, Goodman ZD, Lok AS, Wright EC and Su GL; HALT-C Trial Group, : Serum fibrosis markers are associated with liver disease progression in non-responder patients with chronic hepatitis C. Gut. 59:1401–1409. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Yao HW, Li J, Chen JQ and Xu SY: Inhibitory effect of leflunomide on hepatic fibrosis induced by CCl4 in rats. Acta Pharmacol Sin. 25:915–920. 2004.PubMed/NCBI

16 

Tang X, Yang J and Li J: Accelerative effect of leflunomide on recovery from hepatic fibrosis involves TRAIL-mediated hepatic stellate cell apoptosis. Life Sci. 84:552–557. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Bjorkman DJ, Boschert M, Tolman KG, Clegg DO and Ward JR: The effect of long-term methotrexate therapy on hepatic fibrosis in rheumatoid arthritis. Arthritis Rheum. 36:1697–1701. 1993. View Article : Google Scholar : PubMed/NCBI

18 

Bilasy SE, Essawy SS, Mandour MF, Ali EA and Zaitone SA: Myelosuppressive and hepatotoxic potential of leflunomide and methotrexate combination in a rat model of rheumatoid arthritis. Pharmacol Rep. 67:102–114. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Landsman L, Varol C and Jung S: Distinct differentiation potential of blood monocyte subsets in the lung. J Immunol. 178:2000–2007. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Nahrendorf M, Swirski FK, Aikawa E, Stangenberg L, Wurdinger T, Figueiredo JL, Libby P, Weissleder R and Pittet MJ: The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med. 204:3037–3047. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Wang L, Ma L, Lin Y, Liu X, Xiao L, Zhang Y, Xu Y, Zhou H and Pan G: Leflunomide increases hepatic exposure to methotrexate and its metabolite by differentially regulating multidrug resistance-associated protein Mrp2/3/4 transporters via peroxisome proliferator-activated receptor α activation. Mol Pharmacol. 93:563–574. 2018. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Lin M, Guo R, Su Z, Ke S and Zeng D: Combination leflunomide and methotrexate impedes the recovery of liver fibrosis, partly through inhibition of myeloid cell admittance. Mol Med Rep 19: 1622-1628, 2019.
APA
Lin, M., Guo, R., Su, Z., Ke, S., & Zeng, D. (2019). Combination leflunomide and methotrexate impedes the recovery of liver fibrosis, partly through inhibition of myeloid cell admittance. Molecular Medicine Reports, 19, 1622-1628. https://doi.org/10.3892/mmr.2019.9821
MLA
Lin, M., Guo, R., Su, Z., Ke, S., Zeng, D."Combination leflunomide and methotrexate impedes the recovery of liver fibrosis, partly through inhibition of myeloid cell admittance". Molecular Medicine Reports 19.3 (2019): 1622-1628.
Chicago
Lin, M., Guo, R., Su, Z., Ke, S., Zeng, D."Combination leflunomide and methotrexate impedes the recovery of liver fibrosis, partly through inhibition of myeloid cell admittance". Molecular Medicine Reports 19, no. 3 (2019): 1622-1628. https://doi.org/10.3892/mmr.2019.9821
Copy and paste a formatted citation
x
Spandidos Publications style
Lin M, Guo R, Su Z, Ke S and Zeng D: Combination leflunomide and methotrexate impedes the recovery of liver fibrosis, partly through inhibition of myeloid cell admittance. Mol Med Rep 19: 1622-1628, 2019.
APA
Lin, M., Guo, R., Su, Z., Ke, S., & Zeng, D. (2019). Combination leflunomide and methotrexate impedes the recovery of liver fibrosis, partly through inhibition of myeloid cell admittance. Molecular Medicine Reports, 19, 1622-1628. https://doi.org/10.3892/mmr.2019.9821
MLA
Lin, M., Guo, R., Su, Z., Ke, S., Zeng, D."Combination leflunomide and methotrexate impedes the recovery of liver fibrosis, partly through inhibition of myeloid cell admittance". Molecular Medicine Reports 19.3 (2019): 1622-1628.
Chicago
Lin, M., Guo, R., Su, Z., Ke, S., Zeng, D."Combination leflunomide and methotrexate impedes the recovery of liver fibrosis, partly through inhibition of myeloid cell admittance". Molecular Medicine Reports 19, no. 3 (2019): 1622-1628. https://doi.org/10.3892/mmr.2019.9821
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