Next Article in Journal
Differential Effects of Indoxyl Sulfate and Inorganic Phosphate in a Murine Cerebral Endothelial Cell Line (bEnd.3)
Next Article in Special Issue
The Combined Repetitive Oligopeptides of Clostridium difficile Toxin A Counteract Premature Cleavage of the Glucosyl-Transferase Domain by Stabilizing Protein Conformation
Previous Article in Journal
Type I Interferons as Regulators of Human Antigen Presenting Cell Functions
Previous Article in Special Issue
Staphylococcal enterotoxins in the Etiopathogenesis of Mucosal Autoimmunity within the Gastrointestinal Tract
Article Menu

Export Article

Open AccessArticle
Toxins 2014, 6(6), 1724-1741; doi:10.3390/toxins6061724

Toxic Shock Syndrome Toxin-1-Mediated Toxicity Inhibited by Neutralizing Antibodies Late in the Course of Continual in Vivo and in Vitro Exposure

1
Biomedizinische ForschungsgmbH Lazarettgasse 19/2, Vienna A-1090, Austria
2
Immunology Outpatient Clinic, Schwarzspanierstrasse 15, Vienna A-1090, Austria
*
Author to whom correspondence should be addressed.
Received: 6 February 2014 / Revised: 7 May 2014 / Accepted: 20 May 2014 / Published: 30 May 2014
(This article belongs to the Special Issue Enterotoxins: Microbial Proteins and Host Cell Dysregulation)
View Full-Text   |   Download PDF [553 KB, uploaded 30 May 2014]   |  

Abstract

Toxic shock syndrome (TSS) results from the host’s overwhelming inflammatory response and cytokine storm mainly due to superantigens (SAgs). There is no effective specific therapy. Application of immunoglobulins has been shown to improve the outcome of the disease and to neutralize SAgs both in vivo and in vitro. However, in most experiments that have been performed, antiserum was either pre-incubated with SAg, or both were applied simultaneously. To mirror more closely the clinical situation, we applied a multiple dose (over five days) lethal challenge in a rabbit model. Treatment with toxic shock syndrome toxin 1 (TSST-1) neutralizing antibody was fully protective, even when administered late in the course of the challenge. Kinetic studies on the effect of superantigen toxins are scarce. We performed in vitro kinetic studies by neutralizing the toxin with antibodies at well-defined time points. T-cell activation was determined by assessing T-cell proliferation (3H-thymidine incorporation), determination of IL-2 release in the cell supernatant (ELISA), and IL-2 gene activation (real-time PCR (RT-PCR)). Here we show that T-cell activation occurs continuously. The application of TSST-1 neutralizing antiserum reduced IL-2 and TNFα release into the cell supernatant, even if added at later time points. Interference with the prolonged stimulation of proinflammatory cytokines is likely to be in vivo relevant, as postexposure treatment protected rabbits against the multiple dose lethal SAg challenge. Our results shed new light on the treatment of TSS by specific antibodies even at late stages of exposure. View Full-Text
Keywords: toxic shock syndrome toxin-1; TNF-alpha; IL-2; neutralizing antibody; rabbit animal model; postexposure treatment; continual stimulation toxic shock syndrome toxin-1; TNF-alpha; IL-2; neutralizing antibody; rabbit animal model; postexposure treatment; continual stimulation
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Stich, N.; Model, N.; Samstag, A.; Gruener, C.S.; Wolf, H.M.; Eibl, M.M. Toxic Shock Syndrome Toxin-1-Mediated Toxicity Inhibited by Neutralizing Antibodies Late in the Course of Continual in Vivo and in Vitro Exposure. Toxins 2014, 6, 1724-1741.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top