Blood viscosity and the expression of inflammatory and adhesion markers in homozygous sickle cell disease subjects with chronic leg ulcers.
OBJECTIVE
To determine differences in TNF-α, IL-1β, IL-10, sICAM-1 concentrations, leg hypoxia and whole blood viscosity (WBV) at shear rates of 46 sec(-1) and 230 sec(-1) in persons with homozygous S sickle cell disease (SCD) with and without chronic leg ulceration and in AA genotype controls.


METHODS
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METHODS
fifty-five age-matched participants were recruited into the study: 31 SS subjects without leg ulcers (SSn), 24 SS subjects with leg ulcers (SSu) and 18 AA controls. Haematological indices were measured using an AC.Tron Coulter Counter. Quantification of inflammatory, anti-inflammatory and adhesion molecules was performed by ELISA. Measurement of whole blood viscosity was done using a Wells Brookfield cone-plate viscometer. Quantification of microvascular tissue oxygenation was done by Visible Lightguide spectrophotometry.


RESULTS
TNF-α and whole blood viscosity at 46 sec(-1) and 230 sec(-1) (1.75, 2.02 vs. 0.83, 1.26, p<0.05) were significantly greater in sickle cell disease subjects than in controls. There were no differences in plasma concentration of sICAM-1, IL-1β and IL-10 between SCD subjects and controls. IL-1β (median, IQR: 0.96, 1.7 vs. 0, 0.87; p<0.01) and sICAM-1 (226.5, 156.48 vs. 107.63, 121.5, p<0.005) were significantly greater in SSu group compared with SSn. However there were no differences in TNF-α (2, 3.98 vs. 0, 2.66) and IL-10 (13.34, 5.95 vs. 11.92, 2.99) concentrations between SSu and SSn. WBV in the SSu group at 46 sec(-1) and at 230 Sec 1 were 1.9 (95%CI; 1.2, 3.1) and 2.3 (1.2, 4.4) times greater than in the SSn group. There were no differences in the degree of tissue hypoxia as determined by lightguide spectrophotometry.


CONCLUSIONS
Inflammatory, adhesion markers and WBV may be associated with leg ulceration in sickle cell disease by way of inflammation-mediated vasoocclusion/vasoconstriction. Impaired skin oxygenation does not appear to be associated with chronic ulcers in these subjects with sickle cell disease.
Department of Basic Medical Sciences, Physiology Section, University of the West Indies, Mona, Kingston 7, Jamaica. andre.bowers@uwimona.edu.jm
Andre S
AS
Bowers
Harvey L
HL
Reid
Andre
A
Greenidge
Clive
C
Landis
Marvin
M
Reid
D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications*; D015415:Biomarkers / Q000378:metabolism; D001809:Blood Viscosity; D016022:Case-Control Studies; D002448:Cell Adhesion; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007871:Leg Ulcer / Q000097:blood* / Q000150:complications*; D008297:Male; D010100:Oxygen / Q000378:metabolism; D033081:Shear Strength
D015415:Biomarkers; D016207:Cytokines; D006454:Hemoglobins; D018836:Inflammation Mediators; D007770:L-Lactate Dehydrogenase; D010100:Oxygen