title: Anti-inflammatory role of methotrexate in adjuvant arthritis: effect on substance p and calcitonin gene-related Peptide in thymus and spleen.
abstract: OBJECTIVE
  To investigate the anti-inflammatory effect of methotrexate (MTX) in rats with adjuvant arthritis through its influence on the expression of proinflammatory neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP) in immune organs, thymus and spleen.
  
  
  METHODS
  Phase-I pre-clinical trial.
  
  
  METHODS
  The Aga Khan University, Karachi, from July to December 2003.
  
  
  METHODS
  Adjuvant arthritis was induced in rats by inoculation with heat-killed mycobacteria. One group of arthritic rats (n=6) was treated 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 controls, 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biological and Biomedical Sciences, The Aga Khan University, Karachi.
authors.forename: Jawed Altaf
authors.initials: JA
authors.lastname: Baig
authors.forename: Mohammad Perwaiz
authors.initials: MP
authors.lastname: Iqbal
authors.forename: Rasham
authors.initials: R
authors.lastname: Rehman
authors.forename: Ayaz Alam
authors.initials: AA
authors.lastname: Qureshi
authors.forename: Mahmood
authors.initials: M
authors.lastname: Ahmed