Increased serum fractalkine in systemic sclerosis. Down-regulation by prostaglandin E1.
OBJECTIVE
To evaluate serum levels of fractalkine (FKN), a mediator of leukocyte transmigration, C-reactive protein (CRP) and expression of integrins CD11a and CD49d on peripheral blood lymphocytes in systemic sclerosis (SSc) and to investigate whether they are modulated by intravenous prostaglandin E1 (PGE1).


METHODS
Serum levels of fractalkine and C-reactive protein and expression of CD11a and CD49d on peripheral blood lymphocytes were assessed in 50 SSc patients and in 18 healthy controls. In 25 SSc patients studied parameters were evaluated also after 3 consecutive daily PGE1 infusions (20 microg-40 microg-60 microg) and after 4 weeks.


RESULTS
In SSc fractalkine basal level was significantly higher than in controls (9.04+/-1.79 ng/ml vs. 1.17+/-0.1 ng/ml; p<0.0001) and decreased significantly after PGE1 (5.16+/-1.27 ng/ml, p<0.05). After four weeks fractalkine level was still significantly lower than baseline 7.70+/-2.19 ng/ml (p<0.05). Basal percentage of CD11a (+) nor CD49d (+) lymphocytes in SSc (82.38+/-1.60%, 70.74+/-1.68%, respectively) did not differ from controls (85.73+/-2.04%, 75.62+/-2.48%; respectively, p>0.05). PGE1 treatment resulted in decrease of both CD11a (+) (67.72+/-3.34%, p<0.0001) and CD49d (+) lymphocytes (65.32+/-1.62%, p<0.0001). After 4 weeks the percentage of CD11a (+) and CD49d (+) lymphocytes remained significantly lower than at baseline (77.80+/-2.47% and 65.32+/-1.62%, respectively, both p<0.001). In SSc CRP basal level was significantly higher than in controls (4.70+/-2.01 mg/dl vs. 1.40+/-1.79 mg/dl, p<0.005) and reduced significantly after PGE1 (3.39+/-2.06 mg/dl, p<0.05). After 4 weeks, CRP level (4.38+/-2.19 ng/ml) was significantly lower than baseline (p<0.05).


CONCLUSIONS
Fractalkine may play an important role in the pathogenesis of vascular dysfunction in systemic sclerosis. Prostaglandin E1 down-regulates serum fractalkine level, as well as CD11a and CD49d expression on peripheral blood lymphocytes, which suggests additional mechanisms in which this vasodilatatory agent exerts its efficacy in systemic sclerosis.
Sicinska
J
J
Department of Dermatology, CSK MSWiA, Warsaw, Poland. justyna.sicinska@cskmswia.pl
Gorska
E
E
Cicha
M
M
Kuklo-Kowalska
A
A
Hamze
V
V
Stepien
K
K
Wasik
M
M
Rudnicka
L
L
D000328:Adult; D000527:Alprostadil / Q000008:administration & dosage*; D002097:C-Reactive Protein / Q000032:analysis / Q000187:drug effects; D040881:CD11a Antigen / Q000187:drug effects / Q000378:metabolism; D016022:Case-Control Studies; D054428:Chemokine CX3CL1 / Q000097:blood* / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D039441:Integrin alpha4 / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D045743:Scleroderma, Diffuse / Q000097:blood / Q000188:drug therapy*; D045745:Scleroderma, Limited / Q000097:blood / Q000188:drug therapy*; D014665:Vasodilator Agents / Q000008:administration & dosage*
D040881:CD11a Antigen; D054428:Chemokine CX3CL1; D014665:Vasodilator Agents; D039441:Integrin alpha4; D002097:C-Reactive Protein; D000527:Alprostadil