Trauma-hemorrhage induces increased thymic apoptosis while decreasing IL-3 release and increasing GM-CSF.
Although the thymus is an important organ in the ontogeny of T lymphocytes, little is known about the effects of hemorrhage and/or trauma on this organ. The objective of this study was to determine whether trauma-hemorrhage induces increased thymic apoptosis and, if so, which mediators may be involved. Male C3H/HeN mice underwent either sham operation, hemorrhagic shock (mean artery blood pressure of 35 +/- 5 mmHg for 90 min, followed by blood and fluid resuscitation), fracture of the right tibia, or fracture plus hemorrhage, respectively. At 3 days after the procedure, total viable thymocyte yield, thymocyte apoptosis (flow cytometry), thymus-derived IL-3 (bioassay), and GM-CSF (ELISA) were determined. The results demonstrate that fracture alone induces no significant change in the parameters measured. However, (i) there was a significant decrease in total viable thymocyte yield and an increase in thymocyte apoptosis following hemorrhage or fracture plus hemorrhage; (ii) thymocyte IL-3 release was significantly reduced after hemorrhage as well as fracture plus hemorrhage; (iii) thymus-derived GM-CSF was significantly increased after fracture plus hemorrhage, but not with hemorrhage alone. In conclusion, severe hemorrhage alone or coupled with fracture can induce thymus atrophy via apoptosis. In addition, the decreased IL-3 release suggests that apoptotic thymic involution may be due to the lack of growth factor support. Such dyshomeostasis may contribute to inappropriate/inadequate T cell maturation leading to host immune suppression following trauma-hemorrhage. Increased thymus-derived GM-CSF might be in part responsible for the systemic inflammatory response following trauma-hemorrhage.
Xu
Y X
YX
Department of surgery, Brown University School of Medicine, Providence, Rhode Island, USA.
Wichmann
M W
MW
Ayala
A
A
Cioffi
W G
WG
Chaudry
I H
IH
D000818:Animals; D017209:Apoptosis; D001284:Atrophy; D002452:Cell Count; D003208:Concanavalin A / Q000494:pharmacology; D004249:DNA Damage; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D007377:Interleukin-3 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013978:Tibial Fractures / Q000378:metabolism*
D007377:Interleukin-3; D003208:Concanavalin A; D016178:Granulocyte-Macrophage Colony-Stimulating Factor