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

Summary 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 (25ng.ml ‐1 ), heparin 2.5 i.u.ml ‐1 , heparin with an equal concentration of protamine, and enoxaparin 2.5i.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.