Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Jul;18(sup1):193-197.
doi: 10.1080/14712598.2018.1448381. Epub 2018 Mar 6.

Thymosin beta 4 regulation of actin in sepsis

Justin B Belsky  1 , Emanuel P Rivers  2   3 , Michael R Filbin  4 , Patty J Lee  5 , Daniel C Morris  6
Affiliations
Review

Thymosin beta 4 regulation of actin in sepsis

Justin B Belsky et al. Expert Opin Biol Ther. 2018 Jul.

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.

PubMed Disclaimer

Conflict of interest statement

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

Figures

Figure 1.
Figure 1.
Box and whisker plot comparing median Thymosin Beta 4 levels in plasma. None of the septic shock or non-infectious SIRS group contained Thymosin Beta 4 levels above the lowest detection of the ELISA assay (78 ng/ml).
Figure 2.
Figure 2.
Box and whisker plot comparing median G-actin levels in plasma. Logarithmic scale. G-actin levels were greatest in the Non-infectious SIRS group followed by septic shock and then healthy controls, p < 0.05.
Figure 3.
Figure 3.
Box and whisker plot comparing median plasma levels of F-actin. Septic shock was greater than the non-infectious SIRS group, p < 0.05. None of the healthy control group contained F-actin levels above the lowest detection of the ELISA assay (0.62 ng/ml).
See this image and copyright information in PMC

References

    1. Rhee C, Dantes R, Epstein L, et al. Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009–2014. Jama. 2017;318(13):1241–1249. - PMC - PubMed
    1. Liu V, Escobar GJ, Greene JD, et al. Hospital deaths in patients with sepsis from 2 independent cohorts. JAMA. 2014;312(1 ):90–92. - PubMed
    1. Marshall J Why have clinical trials in sepsis failed? Trends Mol Med. 2014;20(4):195–203. - PubMed
    1. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801–810. - PMC - PubMed
    1. Trzeciak S, Dellinger RP, Parrillo JE, et al. Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock; relationship to hemodynamics, oxygen transport, and survival. Ann Emerg Med. 2007;49(1):88–98. - PubMed