Induction of interleukin-1beta and interleukin-6 gene expression in hypoperfused skeletal muscle of patients with peripheral arterial disease.
BACKGROUND
A growing amount of data supports the role of inflammation in the pathophysiology of atherosclerotic diseases but the cellular source of cytokines has not been clearly identified. Cytokines could be produced by inflammatory cells, activated endothelial and smooth muscle cells, and by the tissue exposed to recurrent ischemia. Accordingly, we evaluated whether hypoperfusion induces gene expression of interleukin (IL)-1beta and IL-6 in the skeletal muscle of patients with peripheral arterial disease and critical limb ischemia.


METHODS
Skeletal muscle biopsies were obtained, during a femoral-distal bypass, from normoperfused (control) and hypoperfused skeletal muscles in 8 patients. Gene expression was assessed by semiquantitative reverse transcriptase-polymerase chain reaction, using glyceraldehyde-phosphate-deydrogenase mRNA levels as a normalization factor.


RESULTS
In the hypoperfused biopsies, the level of IL-1beta gene expression was significantly higher in all but 2 patients (mean upregulation > 8.8 fold, p = 0.043), and the level of IL-6 gene expression was significantly higher in all but 1 patient (mean upregulation > 23.7 fold, p = 0.031).


CONCLUSIONS
We report that IL-1beta and IL-6 gene expression is markedly upregulated in hypoperfused skeletal muscle of patients with critical lower limb ischemia. To our knowledge this is the first report of a local activation of the inflammatory cascade at the level of hypoperfused skeletal muscle. This activation, which could worsen symptoms and tissue viability and be involved in the pathophysiology of reperfusion injury, might be considered as a therapeutic target. It remains to be investigated whether our results may also apply to coronary artery disease.
Testa
M
M
Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy. ma.testa@agora.stm.it
De Ruvo
E
E
Russo
A
A
Citterio
F
F
Serino
F
F
Mangoni
A
A
Capogrossi
M C
MC
Sperti
G
G
D000368:Aged; D000369:Aged, 80 and over; D001157:Arterial Occlusive Diseases / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism*; D007866:Leg / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*
D007375:Interleukin-1; D016209:Interleukin-8