An investigation of the effects of heparin, low molecular weight heparin, protamine, and fentanyl on the balance of pro- and anti-inflammatory cytokines in in-vitro monocyte cultures.
We report a study conducted to determine if drugs given peri-operatively during cardiac surgery could themselves modulate the balance of pro- and anti-inflammatory cytokines. We determined the cytokine response of 10 separate in vitro monocyte cultures to the administration of drugs at concentrations used during cardiac 'surgery:fentanyl (25 ng.ml-1), heparin 2.5 i.u.ml-1, heparin with an equal concentration of protamine, and enoxaparin 2.5 i.u.ml-1. Fentanyl, heparin and low molecular weight heparin (enoxaparin) led to increased tumour necrosis factor alpha but this did not reach statistical significance. Tumour necrosis factor soluble receptor 1 and 2 was not elevated. Interleukin-1 beta was increased by heparin (p < 0.05), whereas interleukin-1 receptor antagonist was increased by fentanyl (p < 0.05). Protamine blocked the heparin-induced increase in tumour necrosis factor alpha and interleukin-1 beta. These data raise the possibility that endogenous and exogenously administered opioids may be partly contributing to the interleukin-1 receptor antagonist response seen during major surgery.
McBride
W T
WT
Department of Anaesthetics, Royal Victoria Hospital, Belfast.
Armstrong
M A
MA
McMurray
T J
TJ
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000925:Anticoagulants / Q000494:pharmacology*; D006348:Cardiac Surgical Procedures; D018929:Cell Culture Techniques; D016207:Cytokines / Q000187:drug effects*; D005283:Fentanyl / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006494:Heparin Antagonists / Q000494:pharmacology; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D011479:Protamines / Q000494:pharmacology; D017472:Receptors, Interleukin-1 / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D000701:Analgesics, Opioid; D000925:Anticoagulants; D016207:Cytokines; D006494:Heparin Antagonists; D006495:Heparin, Low-Molecular-Weight; D007375:Interleukin-1; D011479:Protamines; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D006493:Heparin; D005283:Fentanyl