Differential modulation of interleukin-6 and interleukin-10 by diclofenac in patients undergoing major surgery

Amr Mahdy, Helen Frances Galley, M. A. Abdel-Wahed, K. F. el-Korny, S. A. Sheta, Nigel Robert Webster

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Abstract

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.

Original languageEnglish
Pages (from-to)797-802
Number of pages5
JournalBritish Journal of Anaesthesia
Volume88
Issue number6
DOIs
Publication statusPublished - 2002

Keywords

  • polypeptides, cytokines
  • enzymes, cyclo-oxygenase
  • complications, inflammation
  • polypeptides, interleukin
  • ANTIINFLAMMATORY RESPONSE
  • GENERAL-ANESTHESIA
  • DOWN-REGULATION
  • CYTOKINE
  • SEPSIS
  • IL-10
  • CELLS
  • EXPRESSION
  • MONOCYTES
  • TRAUMA

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