CCL2, CCL3 and CCL5 chemokines in systemic sclerosis: the correlation with SSc clinical features and the effect of prostaglandin E1 treatment.
OBJECTIVE
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.
Department of BioMedicine, University of Florence, Florence, Italy. bandin@hotmail.it
Francesca
F
Bandinelli
Angela
A
Del Rosso
Armando
A
Gabrielli
Roberto
R
Giacomelli
Francesca
F
Bartoli
Serena
S
Guiducci
Marco
M
Matucci Cerinic
D000368:Aged; D000527:Alprostadil / Q000008:administration & dosage*; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood*; D054405:Chemokine CCL3 / Q000097:blood*; D018946:Chemokine CCL5 / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; C111835:CCL2 protein, human; C515429:CCL3 protein, human; C483024:CCL5 protein, human; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D018946:Chemokine CCL5; D000527:Alprostadil