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.