Generation of leukotrienes from human polymorphonuclear granulocytes of severely burned patients

The Ca ionophore A23187-induced leukotriene (LT) release (LTC4, LTB4, 20-OH-LTB4, 20-COOH-LTB4) of human PMN's from severely burned patients (n = 6) was studied by reversed-phase HPLC. The patients' granulocytes demonstrated a decrease (to zero levels) in LT generation postburn. The level of generated LT's resembled that of healthy donors when the patients recovered from their trauma (after day 40 postburn). In contrast, the granulocytes of patients who finally succumbed to their injuries showed poor responsiveness over the total time. An enhanced LTC4 production by granulocytes correlated with an increase in eosinophils within the granulocyte fraction. In addition, the reduced LTB4 production was accompanied by an enhanced LTB4 metabolism to biologically less active products (omega-oxidated metabolites). Thus, the capacity of patients' PMN's to release chemotactic substances was further decreased. The onset of this PMN dysfunction correlated with the onset of invasive microbial growth as determined by the quantitative bacterial analysis of full-thickness biopsy specimens. Our data provide evidence that the altered mediator release of patients' PMN's is closely related to a depressed host defense.