Thymosin-alpha1 promotes the apoptosis of regulatory T cells and survival rate in septic mice

Front Biosci (Landmark Ed). 2011 Jun 1;16:3004-13. doi: 10.2741/3894.

Abstract

Tregs are involved in immune disorder during sepsis; they can lead to a Th2 immune reaction. Their inhibitory effects can help alleviate inflammatory injury, but may also cause secondary immune inhibition. Thymosin-alpha1 is a polypeptide with powerful immunomodulatory activities. Current reports have shown that Thymosin-alpha1 conferred beneficial effects to septic patients. To explore the relationship between Thymosin-alpha1 and Tregs, in this study, we investigated the changing trend in CD4(+)CD25(+)Foxp3(+) T lymphocytes in a CLP septic mouse model. We also investigated the variation of apoptotic rate of CD4(+)CD25(+) T lymphocytes, cytokine variation, and change of model survival rate when Thymosin-alpha1 intervening or not. We observed that the 72-h survival rate was improved, the percentage of CD4(+)CD25(+)Foxp3(+) T lymphocytes decreased and the apoptosis rate of CD4(+)CD25(+) T lymphocytes increased after intervention of Thymosin-alpha1. At same time the expression of pro-inflammation cytokines IL-2, TNF-alpha and anti-inflammatory cytokines IL-10 and TGF-beta were regulated. In conclusion, Thymosin-alpha1 can effectively control the inflammatory response intensity and improve the 72-h survival rate of septic mice. Regulating Tregs may be another important role of Thymosin-alpha1 conditioning the immune reaction in sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cytokines / blood
  • Disease Models, Animal
  • Forkhead Transcription Factors / metabolism
  • Ileum / pathology
  • Immunologic Factors / pharmacology
  • Mice
  • Sepsis / drug therapy*
  • Sepsis / immunology
  • Sepsis / pathology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / pathology
  • Thymalfasin
  • Thymosin / analogs & derivatives*
  • Thymosin / immunology
  • Thymosin / pharmacology

Substances

  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Immunologic Factors
  • Thymosin
  • Thymalfasin