Differential modulation of interleukin-6 and interleukin-10 by diclofenac in patients undergoing major surgery.
BACKGROUND
Prostaglandins modulate cytokine release though increases in cAMP, regulating interleukin (IL) 6 and IL-10. Diclofenac inhibits cyclo-oxygenase activity and hence prostaglandin production. We hypothesized that diclofenac would affect release of IL-6 and IL-10 and modulate the immune response.


METHODS
In a randomized, double-blind, placebo-controlled study, we investigated the effect of diclofenac in patients undergoing major urological surgery. Patients were randomized to receive either diclofenac (50 mg orally every 8 h the day before surgery and 75 mg i.m. every 12 h on the day of surgery, n = 23) or placebo (n = 23). Standardized combined general anaesthesia and epidural analgesia was administered. Serum IL-6, IL-10 and cortisol were measured before surgery and 30 min and 2, 6, 12 and 24 h after skin incision. Temperature, leucocyte count and C-reactive protein concentration were measured before surgery and after 24 h.


RESULTS
IL-6 and IL-10 concentrations increased, reaching peak levels at 12 and 6 h respectively in both groups. At 12 h, the IL-6 concentration was significantly lower in patients receiving diclofenac than in those receiving placebo (P = 0.003). In contrast, IL-10 concentration at 6 h was higher in diclofenac-treated patients (P = 0.008), and this was associated with less pyrexia (P = 0.03), a lower leucocyte count (P = 0.0002) and a lower C-reactive protein concentration (P = 0.0039). Serum cortisol concentration was similar in the two groups of patients until 24 h, when the concentration was lower in patients who received diclofenac (P = 0.002). Cortisol concentration correlated with IL-6 concentration at 24 h.


CONCLUSIONS
Administration of diclofenac was associated with lower IL-6 and higher IL-10 concentrations, and lower leucocyte count, C-reactive protein concentration and temperature. Diclofenac may have an anti-inflammatory role in major surgery.
Mahdy
A M
AM
Academic Unit of Anaesthesia and Intensive Care, University of Aberdeen, Institute of Medical Sciences, Aberdeen AB25 2ZD, UK.
Galley
H F
HF
Abdel-Wahed
M A
MA
el-Korny
K F
KF
Sheta
S A
SA
Webster
N R
NR
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D016753:Interleukin-10 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D007432:Intraoperative Period; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013520:Urologic Surgical Procedures
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D015850:Interleukin-6; D016753:Interleukin-10; D004008:Diclofenac; D002097:C-Reactive Protein; D006854:Hydrocortisone