Anti-inflammatory role of methotrexate in adjuvant arthritis: Effect on substance P and calcitonin gene-related peptide in thymus and spleen

Jawed Altaf Baig, Mohammad Perwaiz Iqbal, Rasham Rehman, Ayaz Alam Qureshi, Mahmood Ahmed

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Objective: To investigate the anti-inflammatory effect of methotrexate (MTX) in rats with adjuvant arthritis through its influence on the expression of proinflammalory neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP) in immune organs, thymus and spleen. Design: Phase-I pre-clinical trial. Place and Duration of Study: The Aga Khan University, Karachi, from July to December 2003. Materials and Method: Adjuvant arthritis was induced in rats by inoculation with heat-killed mycobacteria. One group of arthritic rats (n=6) was ireated with MTX (0.2 mg/kg body weight, subcutaneously) on every 4th day for a period of 18 weeks, while another group of arthritic rats (n-6) was treated with physiological saline served as control. At the end of experiment, animals were sacrificed and thymus and spleen were dissected and prepared for immunohistochemical analysis. The neuronal density of SP and CGRP immunoreactivity in thymus and spleen was assessed by semi-quantitative analysis. Results: There was a marked reduction in hind paw swelling and inflammation in the MTX-treated rats after 18 weeks of treatment. Restoration of joint spaces (tibiotalar and subtalar) was seen after 9 weeks of MTX treatment. CGRP-positive nerve fibres were significantly reduced (p=0.0001) in thymus of rats treated with MTX compared to control rats. SP-positive nerve fibers were also found to be decreased in thymus of rats treated with MTX compared to conlrols, however, the decrease was not statistically significant. The neuronal density of SP and CGRP-immunoreactivity in spleen was not significantly different in MTX-treated and placebo-treated rats. Conclusion: In arthritic rats, MTX significantly reduced CGRP expression in thymus. Suppression of pro-inflammatory neuropeptides, such as CGRP and probably SP could be another mechanism by which MTX produces its anti-inflammatory effect in adjuvant arthritis.

Original languageEnglish
Pages (from-to)490-494
Number of pages5
JournalJournal of the College of Physicians and Surgeons--Pakistan : JCPSP
Volume17
Issue number8
Publication statusPublished - Aug 2007

Keywords

  • Adjuvant arthritis
  • Anti-inflammation
  • Calcitonin gene-related peptide
  • Methotrexate
  • Spleen
  • Substance P
  • Thymus

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