PMID- 24887085
OWN - NLM
STAT- MEDLINE
DCOM- 20150126
LR  - 20211021
IS  - 2072-6651 (Electronic)
IS  - 2072-6651 (Linking)
VI  - 6
IP  - 6
DP  - 2014 May 30
TI  - Toxic shock syndrome toxin-1-mediated toxicity inhibited by neutralizing 
      antibodies late in the course of continual in vivo and in vitro exposure.
PG  - 1724-41
LID - 10.3390/toxins6061724 [doi]
AB  - 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 
      TNFalpha 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.
FAU - Stich, Norbert
AU  - Stich N
AD  - Biomedizinische ForschungsgmbH Lazarettgasse 19/2, Vienna A-1090, Austria. 
      Norbert.Stich@biomed-research.at.
FAU - Model, Nina
AU  - Model N
AD  - Biomedizinische ForschungsgmbH Lazarettgasse 19/2, Vienna A-1090, Austria. 
      Nina.Model@biomed-research.at.
FAU - Samstag, Aysen
AU  - Samstag A
AD  - Immunology Outpatient Clinic, Schwarzspanierstrasse 15, Vienna A-1090, Austria. 
      office@itk.at.
FAU - Gruener, Corina S
AU  - Gruener CS
AD  - Biomedizinische ForschungsgmbH Lazarettgasse 19/2, Vienna A-1090, Austria. 
      Corina.Gruener@biomed-research.at.
FAU - Wolf, Hermann M
AU  - Wolf HM
AD  - Immunology Outpatient Clinic, Schwarzspanierstrasse 15, Vienna A-1090, Austria. 
      hermann.wolf@itk.at.
FAU - Eibl, Martha M
AU  - Eibl MM
AD  - Biomedizinische ForschungsgmbH Lazarettgasse 19/2, Vienna A-1090, Austria. 
      martha.eibl@meduniwien.ac.at.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140530
PL  - Switzerland
TA  - Toxins (Basel)
JT  - Toxins
JID - 101530765
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Antitoxins)
RN  - 0 (Bacterial Toxins)
RN  - 0 (Enterotoxins)
RN  - 0 (Interleukin-2)
RN  - 0 (Mutant Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Superantigens)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (enterotoxin F, Staphylococcal)
SB  - IM
MH  - Animals
MH  - Antibodies, Neutralizing/pharmacology/*therapeutic use
MH  - Antitoxins/pharmacology/*therapeutic use
MH  - Bacterial Toxins/*antagonists & inhibitors/genetics/metabolism/toxicity
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - *Disease Models, Animal
MH  - Enterotoxins/*antagonists & inhibitors/genetics/metabolism/toxicity
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Interleukin-2/genetics/metabolism
MH  - Leukocytes, Mononuclear/cytology/drug effects/immunology/metabolism
MH  - Lymphocyte Activation/drug effects
MH  - Male
MH  - Mutant Proteins/antagonists & inhibitors/metabolism/toxicity
MH  - Rabbits
MH  - Recombinant Proteins/chemistry/metabolism/toxicity
MH  - Shock, Septic/*drug therapy/etiology/immunology/metabolism
MH  - Superantigens/genetics/metabolism/toxicity
MH  - Survival Analysis
MH  - T-Lymphocytes/drug effects/immunology/metabolism
MH  - Toxicokinetics
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC4073126
EDAT- 2014/06/03 06:00
MHDA- 2015/01/27 06:00
PMCR- 2014/06/01
CRDT- 2014/06/03 06:00
PHST- 2014/02/06 00:00 [received]
PHST- 2014/05/07 00:00 [revised]
PHST- 2014/05/20 00:00 [accepted]
PHST- 2014/06/03 06:00 [entrez]
PHST- 2014/06/03 06:00 [pubmed]
PHST- 2015/01/27 06:00 [medline]
PHST- 2014/06/01 00:00 [pmc-release]
AID - toxins6061724 [pii]
AID - toxins-06-01724 [pii]
AID - 10.3390/toxins6061724 [doi]
PST - epublish
SO  - Toxins (Basel). 2014 May 30;6(6):1724-41. doi: 10.3390/toxins6061724.