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

J Surg Res. 2001 Jun 1;98(1):9-15. doi: 10.1006/jsre.2001.6157.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Burns / genetics
  • Burns / metabolism
  • Burns / physiopathology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / metabolism
  • Spleen / metabolism
  • Thymus Gland / metabolism
  • Thymus Gland / physiopathology*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*
  • Up-Regulation

Substances

  • RNA, Messenger
  • Tumor Necrosis Factor-alpha