Effect of low-dose methyl prednisolone on serum cytokine levels following extracorporeal circulation

Abstract

The systemic inflammatory response to cardiopulmonary bypass (CPB) is associated with increased production of cytokines. This systemic inflammatory response characterized by the activation of interleukin-6 (IL-6) and interleukin-8 (IL-8) during and after CPB is well documented. A prospective, randomized, double-blind study was performed so as to understand the effects of low-dose methyl prednisolone sodium succinate (MPSS) on the circulating levels of serum cytokines and clinical outcome. Twenty patients were randomly divided into two groups on the basis of the administration of low-dose (1 mg/kg) MPSS ( n = 10) and placebo ( n = 10) into the pump prime solution. All patients were scheduled to undergo a primary elective coronary artery bypass grafting operation. Patients receiving concurrent corticosteroids, salicylates, dipyridamol or anticoagulants were excluded from the study. Other exclusion criteria were concurrent chronic obstructive pulmonary disease, chronic renal failure, insulin-dependent diabetes, congestive cardiac failure, peptic ulcer history, prior cardiac operations, recent (in a one-month period) myocardial infarction and steroid dependency. Mild systemic hypothermia (30-32°C, rectal) was assured during the CPB. Four blood samples were drawn from the radial artery catheter immediately before starting CPB (T1), following protamine administration (T2) and at 24 (T3) and 48 h (T4) after completion of CPB. In each sample, creatine kinase-myocardial band (CK-MB), white blood cell (WBC), IL-6 and IL-8 levels were measured. IL-6 and IL-8 concentrations were measured by enzyme immunoassay and enzyme-linked immunoabsorbant assay methods. Serum IL-6 T2 and serum IL-6 T3 levels were significantly higher than IL-6 T1 levels in both groups ( p < 0.001) and ( p < 0.01), and there was no significant elevation in serum IL-8 levels in either group. Serum IL-6 levels were significantly higher in the placebo group than in the MPSS group at T3 ( p < 0.009). There was no significant difference in CK-MB T1 levels between the groups. Although there was no significant difference between CK-MB T1 and T2 levels in the MPSS group, the CK-MB T2 and CK-MB T3 levels were significantly higher than T1 levels in the placebo group ( p < 0.001) and ( p < 0.05). There was significant elevation of WBC levels at T2 and T3 in both groups without notable difference between the groups ( p < 0.05). This study has shown that low-dose MPSS suppresses CPB-induced inflammatory response. Further clinical studies (on larger and higher risk groups) may reveal more information on relations between morbidity and cytokine levels which may have some predictive value on clinical outcome following CPB.