The role of programmed cell death (apoptosis) in thymic involution following sepsis
R. A. Barke, S. Roy, R. B. Chapin and R. Charboneau
Department of Surgery, University of Minnesota, Minneapolis.
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-1 beta-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-1
beta-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.
