Induction of interleukin-19 and interleukin-22 after cardiac surgery with cardiopulmonary bypass.
BACKGROUND
Interleukin (IL)-19, IL-20, and IL-22, three novel cytokines in the IL-10 family, have recently been discovered. The biological functions and clinical implications of these cytokines are not clear. We aimed to analyze if serum levels of these cytokines were altered in inflammatory responses of postoperative cardiopulmonary bypass (CPB) and investigate the molecular mechanism involved in cytokine induction.


METHODS
Twenty-five patients undergoing elective aortic-coronary bypass grafting with CPB were enrolled in this study. Blood samples withdrawn at (T1) before anesthesia, (T2) CPB start, (T3) CPB end, (T4) 4 hours post-CPB, (T5) 8 hours post-CPB, (T6) 12 hours post-CPB, (T7) 24 hours post-CPB, and (T8) 48 hours post-CPB were assayed for IL-6, IL-10, IL-19, IL-20, IL-22, and tumor necrotic factor-alpha (TNF-alpha). Transcripts of IL-19, IL-20, and IL-22 from monocytes were analyzed. In vitro, levels of IL-19, IL-20, and IL-22 production in monocytes incubated with IL-6 and TNF-alpha were determined.


RESULTS
The serum levels of IL-19 and IL-22 significantly increased at T3, peaked at T5, and remained increased at T8 (p<0.001). Induction of IL-19 and IL-22 was concomitant with the change in IL-10, IL-6, and TNF-alpha levels. Interleukin-19, IL-20, and IL-22 transcripts in monocytes from patients increased after CPB. In vitro experiments showed that IL-6 and TNF-alpha upregulated IL-19 protein expression in monocytes.


CONCLUSIONS
Serum IL-19 and IL-22 were induced in cardiac surgery with CPB and concomitant with induction of IL-6 and TNF-alpha. The IL-19 and these proinflammatory cytokines may interactively contribute to systemic inflammatory responses after CPB.
Hsing
Chung-Hsi
CH
Institute of Biopharmaceutical Sciences, Tainan, Taiwan.
Hsieh
Mei-Yi
MY
Chen
Wei-Yu
WY
Cheung So
Edmund
E
Cheng
Bor-Chih
BC
Chang
Ming-Shi
MS
D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002478:Cells, Cultured / Q000187:drug effects; D001026:Coronary Artery Bypass; D016207:Cytokines / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D017558:Elective Surgical Procedures; D004797:Enzyme-Linked Immunosorbent Assay; D005112:Extracorporeal Circulation / Q000009:adverse effects / Q000295:instrumentation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D007378:Interleukins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D007387:Internal Mammary-Coronary Artery Anastomosis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000209:etiology* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D000097043:Interleukin-22
D002097:C-Reactive Protein; D016207:Cytokines; D018076:DNA, Complementary; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015850:Interleukin-6; D007378:Interleukins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22; C421250:IL19 protein, human; C422042:interleukin 20