ELEVATED SERUM CYCLOPHILIN LEVELS IN PATIENTS WITH SEVERE SEPSIS

Several cytokines are considered to be important mediators in the path ophysiology of sepsis. Cyclophilins (Cyps), the main binding proteins for the immunosuppressive drug cyclosporine A, have been suggested to function as cytokines. This study was conducted to determine (i) if se rum Cyp levels were elevated in critically ill patients suffering from either sepsis or other life-threatening diseases and (ii) if so, whet her there was an association between Cyp levels and a certain diagnosi s and/or outcome. Serum samples of 45 patients (22 severe sepsis, 23 o ther diagnoses) and 17 healthy controls were prospectively analyzed by an enzymatic assay using the ability of cyclophilins to catalyze cis/ trans isomerisation of peptidyl-prolyl-peptide bonds (PPIase activity) . In addition, western blotting was applied to differentiate both isof orms. PPIase activity was significantly higher in patients with severe sepsis than in patients with other diagnoses (P = 0.004) or in health y subjects (P = 0.001). There was no difference between healthy subjec ts and other critically ill patients (P = 0.067). Elevated PPIase acti vity was associated with high mortality (P = 0.03). It is concluded th at Cyps might play a role, probably as mediators in the pathophysiolog y of sepsis or as symptoms of diagnostic value.