Therapeutic effects of TACI-Ig on collagen-induced arthritis by regulating T and B lymphocytes function in DBA/1 mice

Eur J Pharmacol. 2011 Mar 11;654(3):304-14. doi: 10.1016/j.ejphar.2011.01.002. Epub 2011 Jan 16.

Abstract

To investigate the abnormal function of T and B lymphocytes involved in collagen-induced arthritis in DBA/1 mice and the regulation role of TACI-Ig on T and B lymphocytes, collagen-induced arthritis models were established in DBA/1 mice. Mice were divided randomly into eight groups, including normal, collagen-induced arthritis model, TACI-Ig (0.350, 1.105, 3.333, 10, and 30 mg/kg) and IgG-Fc (10mg/kg) treated groups. The effect of TACI-Ig on collagen-induced arthritis was evaluated by arthritis scores, joints and spleens histopathology, paws radiology, and indices of thymus and spleen. T and B lymphocyte proliferations were assayed by [(3)H]-TdR method. B lymphocyte stimulator and prostaglandin E(2) in serum were assayed by enzyme linked immunosorbent assay. The subsets of T and B lymphocytes were assayed by flow cytometry. Results showed that the onset of paw-swelling was on day 31 after immunization. The peak of inflammation appeared on day 42 and then declined after day 63. Compared with normal mice, collagen-induced arthritis mice have increased arthritis scores, spleen and thymus indices, radiograph scores of joints, and pathology scores of joints and spleens. TACI-Ig could ameliorate these changes and reduce the increased serum level of B lymphocyte stimulator and prostaglandin E(2). Further studies showed that TACI-Ig inhibited T and B lymphocyte proliferation response, and inhibited differentiation and activity of T and B lymphocytes in collagen-induced arthritis mice. In conclusion, TACI-Ig has a good therapeutic action on collagen-induced arthritis mice, which might be related to the regulation of TACI-Ig on inflammation mediators and abnormal function of T and B lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / blood
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / pathology
  • Autoimmunity / drug effects
  • B-Cell Activating Factor / blood
  • B-Lymphocyte Subsets / drug effects
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / pathology
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • Cell Proliferation / drug effects
  • Dinoprostone / blood
  • Joints / drug effects
  • Joints / immunology
  • Joints / pathology
  • Male
  • Mice
  • Recombinant Fusion Proteins / pharmacology*
  • Recombinant Fusion Proteins / therapeutic use
  • Spleen / drug effects
  • Spleen / pathology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • Thymus Gland / drug effects
  • Thymus Gland / pathology

Substances

  • B-Cell Activating Factor
  • Recombinant Fusion Proteins
  • TACI receptor-IgG Fc fragment fusion protein
  • Dinoprostone