Abstract
OBJECTIVE: To test the hypothesis that thymic involution following peritoneal sepsis is secondary to thymocyte programmed cell death. DESIGN: We investigated the temporal response of thymic weight and thymic DNA fragmentation following peritoneal sepsis induced by cecal ligation and puncture in a rat model. We investigated the possible role of decreased interleukin (IL)-2 synthesis in the induction of apoptosis using rat thymocytes in primary culture. Finally, we studied IL-2 gene expression and IL-2 protein synthesis in phytohemagglutinin and IL-1β–treated thymocytes derived from the cecal ligation and puncture model of sepsis. RESULTS: We demonstrated that (1) there is a significant decrease in thymic weight and an increase in thymic DNA fragmentation with the characteristic apoptotic DNA "ladder" fragmentation pattern on agarose gel electrophoresis following peritoneal sepsis; (2) thymocytes in primary culture sustain a significant increase in thymocyte apoptosis following IL-2 withdrawal; and (3) peritoneal sepsis results in inhibition of phytohemagglutinin and IL-1β–induced thymocyte IL-2 messenger RNA accumulation and protein synthesis. CONCLUSIONS: Thymic involution following peritoneal sepsis is associated with increased thymocyte programmed cell death. Thymocyte apoptosis induced by sepsis may be the result, in part, of inhibition of IL-2 gene expression.(Arch Surg. 1994;129:1256-1262)
