Thymosin beta 4 regulation of actin in sepsis

ABSTRACT

Introduction: Sepsis is the dysregulated host response to an infection resulting in life-threatening organ damage. Thymosin Beta 4 is an actin binding protein that inhibits the polymerization of G-actin into F-actin and improves mortality when administered intravenously to septic rats. Thymosin Beta 4 decreases inflammatory mediators, lowers reactive oxygen species, up-regulates anti-oxidative enzymes, anti-inflammatory genes, and anti-apoptotic enzymes making it an interesting protein to study in sepsis.

Areas covered: The authors summarize the current knowledge of actin and Thymosin Beta 4 as it relates to sepsis via a comprehensive literature search.

Expert opinion: Sepsis results in measurable levels of F-actin in the circulation as well as a decreased concentration of Thymosin Beta 4. It is speculated that F-actinemia contributes to microcirculatory perturbations present in patients with sepsis by disturbing laminar flow. Given that Thymosin Beta 4 inhibits the polymerization of F-actin, it is possible that Thymosin Beta 4 decreases mortality in sepsis via the regulation of actin as well as its other anti-inflammatory properties and should be further pursued as a clinical trial in humans with sepsis.

KEYWORDS:

• Actin
• microcirculatory dysfunction
• sepsis
• thymosin beta 4

Article highlights

• Sepsis is the dysregulated host response to a pathogen resulting in life-threatening organ damage.

• Thymosin Beta 4 is an actin binding protein that inhibits the polymerization of globular actin (G-actin) into filamentous actin (F-actin).

• Plasma F-actin is not detectable in a healthy population but is present at measurable levels in patients with septic shock.

• TB4 levels are undetectable in those with septic shock, suggesting that TB4 is consumed allowing for the unregulated polymerization of actin in the bloodstream.

• Excessive F-actin has been shown to have deleterious effects similar to those seen in sepsis.

• Animals treated with Thymosin Beta 4 and then exposed to a sepsis model resulted in decreased mortality when compared to controls suggesting that Thymosin Beta 4 may be a therapeutic option in sepsis by regulating the polymerization of actin.

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Declaration of interest

J Belsky, E Rivers, and D Morris have made the following US patent application: Methods for treating sepsis based on biomarkers including Thymosin Beta 4, G-actin, and F-actin (patent number: US20170307609A1). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

supplementary material

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Funding

This paper has been published as part of a supplement issue covering the proceedings of the Fifth International Symposium on Thymosins in Health and Disease and is funded by SciClone Pharmaceuticals.