The role of programmed cell death (apoptosis) in thymic involution following sepsis.
OBJECTIVE
To test the hypothesis that thymic involution following peritoneal sepsis is secondary to thymocyte programmed cell death.


METHODS
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.
Barke
R A
RA
Department of Surgery, University of Minnesota, Minneapolis.
Roy
S
S
Chapin
R B
RB
Charboneau
R
R
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D004195:Disease Models, Animal; D004587:Electrophoresis, Agar Gel; D005786:Gene Expression Regulation; D007375:Interleukin-1 / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology; D008297:Male; D009929:Organ Size; D010532:Peritoneal Diseases / Q000473:pathology / Q000503:physiopathology*; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000473:pathology / Q000503:physiopathology*; D013950:Thymus Gland / Q000473:pathology*
D007375:Interleukin-1; D007376:Interleukin-2; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D004247:DNA