AN INVESTIGATION OF THE EFFECTS OF HEPARIN, LOW-MOLECULAR-WEIGHT HEPARIN, PROTAMINE, AND FENTANYL ON THE BALANCE OF PROINFLAMMATORY AND ANTIINFLAMMATORY CYTOKINES IN IN-VITRO MONOCYTE CULTURES

We report a study conducted to determine if drugs given peri-operative ly 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 dr ugs at concentrations used during cardiac surgery:fentanyl (25 ng.ml(- 1)), heparin 2. 5 i.u.ml(-1), heparin with an equal concentration of p rotamine, and enoxaparin 2.5 i.u.ml(-1). Fentanyl, heparin and low mol ecular weight heparin (enoxaparin) led to increased tumour necrosis fa ctor alpha but this did not reach statistical significance. Tumour nec rosis factor soluble receptor 1 and 2 was not elevated. Interleukin-1 beta was increased by heparin (p < 0.05), whereas interleukin-1 recept or antagonist was increased by fentanyl (p < 0.05). Protamine blocked the heparin-induced increase in tumour necrosis factor alpha and inter leukin-1 beta. These data raise the possibility that endogenous and ex ogenously administered opioids may be partly contributing to the inter leukin-1 receptor antagonist response seen during major surgery.