HUMAN SEPSIS INCREASES LYMPHOCYTE INTRACELLULAR CALCIUM

Objective. To determine whether free intracellular calcium is increased during human bacterial sepsis. Design Prospective controlled study of lymphocyte free intracellular calcium concentrations from patients with sepsis compared with critically ill nonseptic patients and healthy subjects. Setting. A large multidisciplinary ICU of a university hospital. Patients. Eleven patients with sepsis, six patients after cardiac surgery, six patients with head injury, and 22 healthy control subjects. Interventions. Blood samples obtained for lymphocyte isolation and measurement of free intracellular calcium concentrations. Measurements: Lymphocytes were isolated using Ficoll-paque centrifugation and free intracellular calcium concentrations were measured using the fluorescent dye fara-2. We also evaluated the effect of septic serum, endotoxin, tumor necrosis factor (TNF), and lysophosphatidylcholine on lymphocyte free intracellular calcium concentrations. Main Results. Mean (+/- SEM) lymphocyte free intracellular calcium concentrations were significantly (p < .05) higher in the septic patients (176 +/- 12 nM) compared with cardiac surgical (112 +/- 9 nM), head-injured (110 +/- 11 nM), or healthy control patients (112 +/- 5 nM). Endotoxin (0.1 and 1.0 mg/mL) and TNF (10 and 100 ng/mL) did not alter lymphocyte free intracellular calcium values. Lysophosphatidylcholine (100 and 200 muM) significantly increased lymphocyte free intracellular calcium in a dose-dependent manner. Septic serum had no effect on resting lymphocyte free intracellular calcium concentrations but potentiated the free intracellular calcium response to lysophosphatidylcholine. Conclusions. Lymphocyte intracellular calcium homeostasis is altered during human sepsis. In addition, circulating factors present in septic serum are capable of altering cellular calcium handling.