The present study examines the effect of post-burn endotoxemia on the capacity for the in vitro induction of interleukin-1 (IL-1)β synthesis by either inflammatory or non-inflammatory stimuli. Adherent cell (AC) cultures from patients with severe burns (n = 14, 25-65% total body surface area) were stimulated with LPS, phorbol ester (TPA) or IL-2 and studied simultaneously with intact or LPS-pretreated preparations from normal donors (n = 9). Levels of spontaneously released IL-1β in unstimulated AC cultures from patients and in LPS-pretreated preparations from normal individuals were highly elevated. However, LPS- and IL-2-related IL-1β production in such cultures was significantly decreased (P < 0.01-0.05). In contrast, in the majority of patients' cultures and LPS-pretreated normal AC preparations, TPA-induced IL-1β production remained relatively unaffected. In all patients studied, reduced capacity for the LPS-induced IL-1 production was observed concurrently with a significant (P < 0.05) elevation in plasma endotoxin content. Diminished secretion of IL-1β coincided also with a profound reduction of IL-2-dependent IFNγ production in patient cultures and in LPS-pretreated normal cultures. Thus, in the burn patient, endotoxemia-related specific desensitization may develop and, combined with other intrinsic mechanisms, restrict the pathophysiological sequelae of continuous bacterial stimulation.
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