The effect of infliximab on chemokines in patients with rheumatoid arthritis

Clin Rheumatol. 2007 Jul;26(7):1088-93. doi: 10.1007/s10067-006-0453-5. Epub 2006 Nov 17.

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by infiltration of lymphocytes, macrophages, and plasma cells into synovial membrane. The chemokines family promotes chemotactic activity in various leukocyte cell types. Chemokines thus play an essential role in the pathological formation of RA. The aim of the present study was to evaluate the influence of infliximab on serum levels of various chemokines. Twenty-four RA patients were involved in this study, which took place between March 2003 and February 2006. Infliximab was administered by intravenous infusion at a dosage of 3 mg/kg. All patients underwent general and physical examinations and routine blood and urinary analysis at the baseline, at 14 weeks, and at 30 weeks after the initial treatment. To determine whether serum and synovial fluid from RA also contained significant levels of chemokines compared with osteoarthritis patients (OA), GRO-alpha, MIP-1alpha, MIP-1beta and regulated on activation normal T cell expressed and secreted (RANTES) levels of serum and synovial fluid were measured by ELISA in 20 RA patients and 20 OA patients. GRO-alpha, MIP-1beta, and RANTES levels were significantly higher in RA compared with normal volunteers, while MIP-1alpha levels showed no significant differences. The mean GRO-alpha levels in serum from RA patients treated with infliximab decreased significantly after the initial treatment. The mean RANTES and MIP-1beta levels did not change significantly after the treatment. Infliximab treatment significantly lowered the serum GRO-alpha levels of RA patients. GRO-alpha is one of the crucial cytokines affected by infliximab treatment. The blocking therapy of RANTES and MIP-1beta combined with infliximab treatment may have an additional effect without competition in the TNFalpha cascade.

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Biomarkers / blood
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5 / blood
  • Chemokine CXCL1
  • Chemokines / blood*
  • Chemokines, CXC / blood
  • Drug Therapy, Combination
  • Female
  • Humans
  • Infliximab
  • Injections, Intravenous
  • Macrophage Inflammatory Proteins / blood
  • Male
  • Middle Aged
  • Osteoarthritis / blood
  • Prednisolone / therapeutic use
  • Synovial Fluid / drug effects
  • Synovial Fluid / metabolism

Substances

  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Biomarkers
  • CXCL1 protein, human
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokine CXCL1
  • Chemokines
  • Chemokines, CXC
  • Macrophage Inflammatory Proteins
  • Prednisolone
  • Infliximab