Abstract
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.
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.
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.
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.
Br J Anaesth 2002; 88: 797–802