Volume 3 Supplement 2

21st European Workshop for Rheumatology Research

Open Access

Thymosin beta4 sylphoxide: potential role in resolution of inflammation?

  • JD Young1,
  • JA Gracie1,
  • RD Stevenson1,
  • AJ Lawrence1,
  • FY Liew2 and
  • IB McInnes1
Arthritis Research & Therapy20013(Suppl 2):P099

https://doi.org/10.1186/ar268

Received: 15 January 2001

Published: 26 January 2001

Background

Thymosin beta 4 sulphoxide (Tb4so) has previously been shown to be produced by glucocorticoid-treated monocytes (1). This highly conserved intracellular peptide possesses 'moonlighting' functions in the modulation of inflammatory responses, and may represent a natural down-regulator of inflammation in vivo. We have investigated the mechanisms of action of Tb4so primarily on neutrophils by studying its effects on in vitro and in vivo models.

Methods

Effect of Tb4so on assays of neutrophil function included chemotaxis and respiratory burst. Apoptosis was measured as Annexin-V/PI binding by FACS and macrophages were stained for phagocytic uptake of apoptotic neutrophils by the presence of neutrophil-specific myeloperoxidase. In vivo, the effect of administration of Tb4so on carrageenan-induced inflammation was eplored.

Results

Tb4so significantly inhibited fMLP-induced chemotaxis (P < 0.005) and respiratory burst of human neutrophils in a dose dependent manner (100% vs 23%, P < 0.05). Further, it increased the rate of apoptosis in neutrophils (20.5 ± 1.9%, P < 0.05) and their subsequent phagocytic uptake by macrophages. In vivo, Tb4so was a potent inhibitor of neutrophil mediated carrageenan-induced inflammation in BALB/c mice (1.2 mm vs 0.6 mm P < 0.001 at 24 h).

Conclusions

Tb4so is an anti-inflammatory peptide that down-regulates neutrophil mediated inflammation. The mechanism of action appears to be, at least in part, via induction of neutrophil apoptosis and their clearance by phagocytic macrophages. These results suggest therapeutic potential for Tb4so.

Authors’ Affiliations

(1)
Centre for Rheumatic Diseases, University Department of Medicine, Royal Infirmary
(2)
Department of Immunology, University of Glasgow

References

  1. Young , et al: Nature Med. 1999, 5: 1424-10.1038/71002.View ArticlePubMedGoogle Scholar

Copyright

© BioMed Central Ltd 2001

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