TRAUMA-HEMORRHAGE INDUCES INCREASED THYMIC APOPTOSIS WHILE DECREASINGIL-3 RELEASE AND INCREASING GM-CSF

Although the thymus is an important organ in the ontogeny of T lymphoc ytes, little is known about the effects of hemorrhage and/or trauma on this organ. The objective of this study was to determine whether trau ma-hemorrhage induces increased thymic apoptosis and, if so, which med iators may be involved. Male C3H/HeN mice underwent either sham operat ion, hemorrhagic shock (mean artery blood pressure of 35 +/- 5 mmHg fo r 90 min, followed by blood and fluid resuscitation), fracture of the right tibia, or fracture plus hemorrhage, respectively. At 3 days afte r the procedure, total viable thymocyte yield, thymocyte apoptosis (fl ow cytometry), thymus-derived IL-3 (bioassay), and GM-CSF (ELISA) were determined. The results demonstrate that fracture alone induces no si gnificant change in the parameters measured. However, (i) there was a significant decrease in total viable thymocyte yield and an increase i n thymocyte apoptosis following hemorrhage or fracture plus hemorrhage ; (ii) thymocyte IL-3 release was significantly reduced after hemorrha ge as well as fracture plus hemorrhage; (iii) thymus-derived GM-CSF wa s significantly increased after fracture plus hemorrhage, but not with hemorrhage alone. In conclusion, severe hemorrhage alone or coupled w ith 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 c ontribute to inappropriate/inadequate T cell maturation leading to hos t immune suppression following trauma-hemorrhage. Increased thymus-der ived GM-CSF might be in part responsible for the systemic inflammatory response following trauma-hemorrhage. (C) 1997 Academic Press.