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

Research output: Contribution to journalArticle

38 Citations (Scopus)

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

Cite this

Differential modulation of interleukin-6 and interleukin-10 by diclofenac in patients undergoing major surgery. / Mahdy, Amr; Galley, Helen Frances; Abdel-Wahed, M. A.; el-Korny, K. F.; Sheta, S. A.; Webster, Nigel Robert.

In: British Journal of Anaesthesia, Vol. 88, No. 6, 2002, p. 797-802.

Research output: Contribution to journalArticle

Mahdy, Amr ; Galley, Helen Frances ; Abdel-Wahed, M. A. ; el-Korny, K. F. ; Sheta, S. A. ; Webster, Nigel Robert. / Differential modulation of interleukin-6 and interleukin-10 by diclofenac in patients undergoing major surgery. In: British Journal of Anaesthesia. 2002 ; Vol. 88, No. 6. pp. 797-802.
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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.",
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T1 - Differential modulation of interleukin-6 and interleukin-10 by diclofenac in patients undergoing major surgery

AU - Mahdy, Amr

AU - Galley, Helen Frances

AU - Abdel-Wahed, M. A.

AU - el-Korny, K. F.

AU - Sheta, S. A.

AU - Webster, Nigel Robert

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

KW - polypeptides, cytokines

KW - enzymes, cyclo-oxygenase

KW - complications, inflammation

KW - polypeptides, interleukin

KW - ANTIINFLAMMATORY RESPONSE

KW - GENERAL-ANESTHESIA

KW - DOWN-REGULATION

KW - CYTOKINE

KW - SEPSIS

KW - IL-10

KW - CELLS

KW - EXPRESSION

KW - MONOCYTES

KW - TRAUMA

U2 - 10.1093/bja/88.6.797

DO - 10.1093/bja/88.6.797

M3 - Article

VL - 88

SP - 797

EP - 802

JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

SN - 0007-0912

IS - 6

ER -