Down regulation of anti-inflammatory cytokine interleukin (IL-10) increases morbidity and mortality following routine coronary artery bypass grafts
A El-Gamel, S Quershi, J Hutchinson, NA Yonan, AK Deiraniya, IV Hutchinson.
Cardiothoracic Department, Wythenshawe Hospital, Manchester.
Background: The release of inflammatory cytokines following CPB initiates a severe inflammatory response. IL-10 ia an anti-inflammatory and an imunosuppressive cytokine, which may reduce the inflammatory response to bypass. We undertook this study to establish the IL-10 response to bypass and its relation to clinical outcomes.
Methods: We prospectively studied 100 consecutive patients who underwent routine CABG. Gamma interferon (a marker for inflammatory response) and IL-10 (a marker for anti-inflammatory response) were measured before bypass, at 30 minutes, at the end of bypass and 24 hours postoperatively using specific ELISA assay. We also cultures leukocytes from all samples stimulated with Con A. DNA were also used to determine the genotype in the IL-10 gene promoter region. Cell samples were exposed to trasylol, adrenaline, noradrenaline, atenolol, bradykinin and notroglycerine to establish in vitro response of cytokine release to differenet drugs used in cardiac operations. DNA was isolated and amplified by PCR. Samples were genotyped for IL-10 by using sequence specific oligonucleotide probe. Clinical data regarding the development of post bypass inflammatory syndrome (ARDS, low SVR) and infectious complications were prospectively collected.
Results: Thirteen patients (Group A) developed post bypass complications (n=9 low SVR, n=4 ARDS), 5 patients developed postoperative infection (Group B n=2 chest, n=3 wound infections), 4 patients died (n=1 low SVR, 3 ARDS), 87 patients had no complications (Group C). There was significant increase in the release of interferon gamma in response to bypass P<0.01 but without significant interpatient variations. Group A had significantly lower serum levels of IL-10 before and during CPB in comparison to Group C. None of the above mentioned drugs have an effect on the release of both IL-10 and interferon gamma. Post operative PaO2/FiO2 ratio correlated positively with IL-10 levels (r2 = 0.8, P<0.03)
Conclusions: IL-10 production is induced by CPB. Low IL-10 response to bypass is associated with post bypass inflammatory syndrome and higher mortality, this may predict the need for prophylactic anti-inflammatory treatment.
