Parallel self-induction of TNF-alpha and apoptosis in the thymus of mice after burn injury

BACKGROUND: Burn injury often causes multiple organ failure as well as skin damage. Several studies suggest that TNF-alpha plays an important role in postinjury immunosuppression by altering lymphoid tissues. We investigated the regulation of TNF-alpha expression and apoptosis in the spleen and thymus of mice after burn injury. MATERIALS and METHODS: C57BLKS/J mice were subjected to 18% TBSA full-thickness burn and the spleen and thymus were harvested at various time points (3 h to 29 days). The expression of TNF-alpha mRNA and protein in tissue extracts was analyzed by RT-PCR and ELISA. Apoptosis was measured by flow cytometry using annexin V staining. RESULTS: Burn injury induced TNF-alpha mRNA expression in the thymus at Day 1 and it returned to the basal levels at Day 14 and thereafter. Similarly, TNF-alpha mRNA up-regulation peaked between Day 1 and Day 3 in the spleen. Induction of TNF-alpha protein peaked at Day 1 in the thymus, whereas, TNF-alpha protein was unchanged in the spleen after burn injury. There was a twofold increase in apoptotic cells at Day 1 in the thymus, which is consistent with mRNA and protein data. In contrast, burn injury did not change apoptotic events in the spleen. CONCLUSIONS: The parallel induction of TNF-alpha mRNA, TNF-alpha protein, and apoptosis suggests that TNF-alpha may contribute to immunosuppression after burn injury by inducing apoptosis in the thymus.