Altered cyclooxygenase-2 expression and nitric oxide metabolism following major elective surgery.
OBJECTIVE
Postoperative variation in immune function leads to increased susceptibility to infections. Cyclooxygenase-2 (COX-2)-generated Prostaglandin-E(2) (PGE(2)), which signals through the PGE(2) receptor (EP receptor), as well as nitric oxide metabolites (NOx), appear to be important in postoperative immune dysfunction. It is unclear, however, how these substrates and receptors change over time. This study was conducted to evaluate postoperative changes in inflammatory mediator production and monocyte COX-2 and EP receptor expression.


METHODS
Nineteen patients had blood drawn preoperatively and up to 1 week postoperatively. Plasma NOx levels were measured. Peripheral blood mononuclear cell (PBMC) COX-2 and EP receptor mRNA expression were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). PBMC PGE(2), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and IL-10 productions were evaluated by enzyme-linked immunosorbent assay (ELISA) kits. Statistical analyses were by ANOVA and Student's t tests.


RESULTS
Postoperatively, PBMC mean PGE(2) and IL-6 productions were significantly increased at all time points. Mean TNF-alpha production was maximal on postoperative day 2, while mean IL-10 production was unchanged. Mean circulating NOx levels demonstrated a biphasic response decreasing early postoperatively and normalizing at postoperative day (POD) 7. PBMC COX-2 enzyme and EP receptor mRNA expression were unchanged.


CONCLUSIONS
Altered PBMC PGE(2) production and plasma NOx levels support a role for altered macrophage activity, which may contribute to immune dysfunction in the postoperative period.
Maddali
Sirish
S
Weill Medical College of Cornell University/New York Presbyterian Hospital, Department of Surgery, New York, NY 10021, USA.
Stapleton
Philip P
PP
Freeman
Tracy A
TA
Yan
Zhaoping
Z
Duff
Michael
M
Smyth
Gordon P
GP
Daly
John M
JM
D000328:Adult; D000368:Aged; D001772:Blood Cell Count; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D011184:Postoperative Period; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000097:blood; D018078:Receptors, Prostaglandin E / Q000235:genetics; D013514:Surgical Procedures, Operative
D016207:Cytokines; D007527:Isoenzymes; D008565:Membrane Proteins; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone