PLASMA LEPTIN LEVELS ARE INCREASED IN SURVIVORS OF ACUTE SEPSIS - ASSOCIATED LOSS OF DIURNAL RHYTHM IN CORTISOL AND LEPTIN SECRETION

Recent animal and human studies have suggested that leptin secretion i s closely linked to the functions of the hypothalamic-pituitary-adrena l (HPA) axis and the immune system, both of which are crucial in influ encing the course and outcome of critical illness. Therefore, we measu red basal plasma leptin levels and examined the circadian secretion of leptin, in parallel with the hormones of the HPA axis and a key cytok ine, interleukin-6, in critically ill patients with acute sepsis. Sixt een critically ill patients from the University of Leipzig Intensive C are Unit were recruited for this study. All of these patients fulfille d the standard diagnostic criteria for sepsis. Plasma leptin levels we re measured in all patients and controls at 09:00. In addition, in a s ubgroup of eight critically ill patients and all of the nine controls plasma leptin, cortisol, ACTH and interleukin-6 concentrations were me asured every 4 hours for 24 hours. Mean plasma leptin levels were thre e-fold higher (18.9 +/- 4.5 ng/ml) in critically ill patients than con trols (3.8 +/- 1.0 ng/ml, p<0.05). Similarly, ACTH levels were lower ( 7.8 +/- 3.4 pmol/l) in patients than in controls (17.1 +/- 1.5 pmol/l, p<.001), while plasma cortisol levels were increased (947.6 +/- 144 n mol/l) in patients compared to controls (361.1+/-29, p<0.001). Morning plasma interleukin-6 levels were markedly elevated in all patients wi th sepsis (1238.0+/-543.1 pg/ml) versus controls (6.4 +/- 1.7, p<0.001 ). The controls exhibited a nyctohemeral fluctuation in plasma leptin levels with peak levels at 23:00; in contrast septic patients, had no nocturnal rise of leptin. In healthy controls, plasma leptin and corti sol had reciprocal circadian rhythms with high nocturnal leptin levels and low nocturnal cortisol concentrations; in critically ill patients , this relation was abolished. Mean leptin levels were three-fold high er in patients who survived the septic episode (25.5+/-6.2, n=10) than in non-survivors (8.0+/-3.7, n=6, p<0.01). We conclude that in additi on to its function as an anti-obesity factor, leptin may play a role i n a severe stress state such as acute sepsis.