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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Am+Heart+Assoc
2015 ; 4
(8
): e002128
Nephropedia Template TP
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English Wikipedia
Colchicine Acutely Suppresses Local Cardiac Production of Inflammatory Cytokines
in Patients With an Acute Coronary Syndrome
#MMPMID26304941
Martínez GJ
; Robertson S
; Barraclough J
; Xia Q
; Mallat Z
; Bursill C
; Celermajer DS
; Patel S
J Am Heart Assoc
2015[Aug]; 4
(8
): e002128
PMID26304941
show ga
BACKGROUND: Interleukin (IL)-1?, IL-18, and downstream IL-6 are key inflammatory
cytokines in the pathogenesis of coronary artery disease. Colchicine is believed
to block the NLRP3 inflammasome, a cytosolic complex responsible for the
production of IL-1? and IL-18. In vivo effects of colchicine on cardiac cytokine
release have not been previously studied. This study aimed to (1) assess the
local cardiac production of inflammatory cytokines in patients with acute
coronary syndromes (ACS), stable coronary artery disease and in controls; and (2)
determine whether acute administration of colchicine inhibits their production.
METHODS AND RESULTS: Forty ACS patients, 33 with stable coronary artery disease,
and 10 controls, were included. ACS and stable coronary artery disease patients
were randomized to oral colchicine treatment (1 mg followed by 0.5 mg 1 hour
later) or no colchicine, 6 to 24 hours prior to cardiac catheterization. Blood
samples from the coronary sinus, aortic root (arterial), and lower right atrium
(venous) were collected and tested for IL-1?, IL-18, and IL-6 using ELISA. In ACS
patients, coronary sinus levels of IL-1?, IL-18, and IL-6 were significantly
higher than arterial and venous levels (P=0.017, <0.001 and <0.001,
respectively). Transcoronary (coronary sinus-arterial) gradients for IL-1?,
IL-18, and IL-6 were highest in ACS patients and lowest in controls (P=0.077,
0.033, and 0.014, respectively). Colchicine administration significantly reduced
transcoronary gradients of all 3 cytokines in ACS patients by 40% to 88%
(P=0.028, 0.032, and 0.032, for IL-1?, IL-18, and IL-6, respectively).
CONCLUSIONS: ACS patients exhibit increased local cardiac production of
inflammatory cytokines. Short-term colchicine administration rapidly and
significantly reduces levels of these cytokines.