TY - JOUR
T1 - Anti-inflammatory role of methotrexate in adjuvant arthritis
T2 - Effect on substance P and calcitonin gene-related peptide in thymus and spleen
AU - Baig, Jawed Altaf
AU - Iqbal, Mohammad Perwaiz
AU - Rehman, Rasham
AU - Qureshi, Ayaz Alam
AU - Ahmed, Mahmood
PY - 2007/8
Y1 - 2007/8
N2 - 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.
AB - 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.
KW - Adjuvant arthritis
KW - Anti-inflammation
KW - Calcitonin gene-related peptide
KW - Methotrexate
KW - Spleen
KW - Substance P
KW - Thymus
UR - http://www.scopus.com/inward/record.url?scp=63149180299&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:63149180299
SN - 1022-386X
VL - 17
SP - 490
EP - 494
JO - Journal of the College of Physicians and Surgeons--Pakistan : JCPSP
JF - Journal of the College of Physicians and Surgeons--Pakistan : JCPSP
IS - 8
ER -