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.


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.
Cho
K
K
Department of Surgery, Shriners Hospitals for Children Northern California, Sacramento, California 95817, USA.
Adamson
L K
LK
Greenhalgh
D G
DG
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002056:Burns / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha