Effects of inflammatory cytokines on vascular tone.
OBJECTIVE
To assess the direct effects of the inflammatory cytokines interleukin-2 (IL-2), interleukin-6 (IL-6) and interleukin-8 (IL-8) on vascular smooth muscle contraction.


METHODS
Smooth muscle contractility was studied in the thoracic aorta isolated from male Sprague-Dawley rats. Syntheses of cAMP and nitric oxide (NO) were investigated in cultured rat vascular smooth muscle cells (VSMC).


RESULTS
Pretreatment of the rings with IL-6 (10 ng/ml) for 180 min caused a significant inhibition of their contraction in response to 10(-5) M phenylephrine, wile Il-2 (10 ng/ml) and IL-8 (100 ng/ml) showed no significant effect on the contraction. The inhibitory effect of IL-6 exhibited a dose-dependency (0.1 approximately 10 ng/ml). In cultured rat VSMC, synthesis of cAMP was increased time-dependently by IL-6, while IL-2 and IL-8 failed to show any significant effects. IL-2, IL-6 and IL-8 did not affect the production of nitrite, a stable metabolite of NO, by VSMC.


CONCLUSIONS
IL-6, but not IL-2 and IL-8, is a potent inhibitor of vascular contraction, which effect is mediated through the increased cAMP synthesis.
Ohkawa
F
F
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Ikeda
U
U
Kanbe
T
T
Kawasaki
K
K
Shimada
K
K
D000818:Animals; D001011:Aorta; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D007376:Interleukin-2; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D000242:Cyclic AMP