CCL2, CCL3 and CCL5 chemokines in systemic sclerosis: the correlation with SSc clinical features and the effect of prostaglandin E1 treatment

Clin Exp Rheumatol. Mar-Apr 2012;30(2 Suppl 71):S44-9. Epub 2012 May 29.

Abstract

Objectives: Chemokines favour leukocyte homing and participate actively in inflammation and accumulation of extracellular matrix. The aim of our work is to assess in patients with systemic sclerosis (SSc) the serum levels of CC chemokines: CCL2 monocyte chemotactic protein-1 (MCP-1/CCL2), CCL5 'regulated upon activation, normal T expressed and secreted' (RANTES/CCL5) and CCL3 'macrophage inflammatory protein 1 α' (MIP1α/CCL3), their associations with clinical characteristics and modulation by infusions of the prostaglandin E1 (PGE1) analogue, alprostadil alpha-cyclodextrin.

Methods: Serum levels of MCP1/CCL2, RANTES/CCL5 and MIP1α/CCL3 were studied by ELISA in 40 patients with SSc (34 lSSc, 6 dSSc) before and after 3 consecutive daily PGE1 infusions (60 μg) and compared to 30 healthy controls. We recorded clinical (age, duration of disease, ulcers, teleangectasias, calcinosis, skin score [mRSS], capillaroscopy pattern, heart and lung involvement) and immunological characteristics (ANA/ACA/Scl70) of patients.

Results: MCP1/CCL2, RANTES/CCL5 and MIP1α/CCL3 levels were significantly higher in SSc patients than in controls and significantly decreased after PGE1 treatment. MCP-1 levels, higher in dSSc and Scl 70 positive patients, correlated with mRSS.

Conclusions: The high levels of circulating chemokines might support a role of MCP1/CCL2, RANTES/CCL5 and MIP1α/CCL3 in SSc pathogenesis and the correlation of MCP-1 with the extent of skin fibrosis might imply its involvement in the development of fibrosis in SSc. PGE1 down-regulates serum MCP1/CCL2 and RANTES/CCL5 levels, suggesting its possible additional effect on inflammation and cell trafficking in SSc.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Alprostadil / administration & dosage*
  • Analysis of Variance
  • Biomarkers / blood
  • Case-Control Studies
  • Chemokine CCL2 / blood*
  • Chemokine CCL3 / blood*
  • Chemokine CCL5 / blood*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Italy
  • Male
  • Middle Aged
  • Scleroderma, Systemic / blood
  • Scleroderma, Systemic / diagnosis
  • Scleroderma, Systemic / drug therapy*
  • Scleroderma, Systemic / immunology*
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • CCL2 protein, human
  • CCL3 protein, human
  • CCL5 protein, human
  • Chemokine CCL2
  • Chemokine CCL3
  • Chemokine CCL5
  • Alprostadil