Increased levels of C-reactive protein and interleukin-6 in hyperhomocysteinemic subjects.
OBJECTIVE
Elevated plasma homocysteine concentration is considered to be an independent risk factor for cardiovascular disease. However, the mechanisms by which hyperhomocysteinemia are related to vascular disease are unclear. High-sensitivity C-reactive protein (CRP), a marker of inflammation, has been reported to be an independent predictor of future myocardial infarction among clinically healthy individuals. Interleukin (IL)-6 is a regulator of CRP and has a key role in initiation of inflammation. The aim of this study was to investigate whether individuals with increased plasma homocysteine concentrations have altered levels of serum CRP and IL-6.


METHODS
Serum concentrations of CRP and IL-6 were measured in 39 individuals with hyperhomocysteinemia and in 39 control subjects matched for gender, age and body mass index (BMI). In addition, the inflammatory effect of IL-6 on peripheral blood mononuclear cells was measured.


RESULTS
Compared to controls, hyperhomocysteinemic subjects have elevated serum levels of CRP and IL-6 (p < or =0.001 and p < 0.005, respectively). Importantly, this raised level of IL-6 was also seen in hyperhomocysteinemic individuals without accompanying hypercholesterolemia or cardiovascular disease. IL-6 increased the release of monocyte chemoattractant protein-1 from peripheral blood mononuclear cells, with particularly enhancing effects in cells from patients with hyperhomocysteinemia.


CONCLUSIONS
These data suggest that enhanced inflammation may be associated with homocysteine-related cardiovascular disease, possibly involving IL-6-related mechanisms.
Holven
K B
KB
The Lipid Clinic, Rikshospitalet University Hospital, NO-0027 Oslo, Norway. kirsten.holven@medisin.uio.no
Aukrust
P
P
Retterstol
K
K
Hagve
T A
TA
Mørkrid
L
L
Ose
L
L
Nenseter
M S
MS
D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000097:blood / Q000150:complications; D018932:Chemokine CCL2 / Q000378:metabolism; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications; D020138:Hyperhomocysteinemia / Q000097:blood* / Q000150:complications; D015850:Interleukin-6 / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D002097:C-Reactive Protein