Effect of methotrexate on inflammatory cells redistribution in experimental adjuvant arthritis

Rheumatol Int. 2012 Nov;32(11):3517-23. doi: 10.1007/s00296-011-2177-3. Epub 2011 Nov 15.

Abstract

The aim of this study was to evaluate the morphological changes in the spleen, the thymus and the knee joints of rats with experimental adjuvant arthritis induced by Mycobacterium butyricum in the incomplete Freund's adjuvant and the effect of treatment with methotrexate (MTX). Particular attention was aimed on the redistribution of granulocytes in the tissues during the inflammatory process. Clinical parameters, e.g., joint edema, body weight and of gamma glutamyl transferase (GGT) activity as an inflammatory marker, have also been determined. Induction of adjuvant arthritis caused a significant decrease in granulocyte number in the spleen and vice versa a significant increase in the knee joints, but without significant changes in the thymus. Treatment with methotrexate reversed this phenomenon by increasing the granulocyte number in the spleen and decreasing it in knee joints. MTX decreased the joint edema as well as the activity of GGT in the spleen, modified the size of the white pulp of the spleen and increased the cortex/medulla ratio in the thymus. The observed changes support the anti-inflammatory and immunomodulatory properties of MTX supporting its use as the first-line medication in patients with rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antirheumatic Agents / pharmacology*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / enzymology
  • Arthritis, Experimental / pathology
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / enzymology
  • Arthritis, Rheumatoid / pathology
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / enzymology
  • Cartilage, Articular / pathology
  • Granulocytes / drug effects*
  • Granulocytes / enzymology
  • Granulocytes / pathology
  • Knee Joint / drug effects
  • Knee Joint / enzymology
  • Knee Joint / pathology
  • Male
  • Methotrexate / pharmacology*
  • Methotrexate / therapeutic use
  • Rats
  • Rats, Inbred Lew
  • Spleen / drug effects
  • Spleen / enzymology
  • Spleen / pathology
  • Synovial Membrane / drug effects
  • Synovial Membrane / enzymology
  • Synovial Membrane / pathology
  • Thymus Gland / drug effects
  • Thymus Gland / enzymology
  • Thymus Gland / pathology
  • gamma-Glutamyltransferase / metabolism

Substances

  • Antirheumatic Agents
  • gamma-Glutamyltransferase
  • Methotrexate