Dataset: The Complement System and the CD14/TLR4/MD2 Complex as Targets for Therapy in Sepsis, 2016

Abstract

The aim of this project was to develop a new therapeutic regime in conditions where the congenital immune system is over-activated and causes serious disease, as seen by sepsis (blood poisoning). Previous studies showed that inhibition of two important branches of the immune system, the complement system and the TRL system, inhibits the activation triggered by bacteria and other foreign substances in the test tube. In particular, combined inhibition of these systems gives a good effect. In this project it was found that a substance called coversin (OmCI) effectively inhibits complement factor 5 in both pigs and human beings. Further, the study worked with an antibody targeting CD14, a central molecule in the TLR system, and compared this to other inhibitors of the TLR family, such as anti-MD2. It was found that inhibition of CD14 is particularly effective in inhibiting activation and that the combination of inhibiting complement and CD14 is particularly effective in sepsis in pigs. The latest work published in the project, revealed to a large degree why clinical trials conducted to treat blood poisoning with the inhibition of the innate immune system (TLR4 / MD2) have not worked. This worked was published in the 'Journal of Infectious Diseases'.

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http://www.nsd.uib.no/nsd/english/orderform.html

Variable Groups

Full Title

The Complement System and the CD14/TLR4/MD2 Complex as Targets for Therapy in Sepsis, 2016

Identification Number

NSD2430

Authoring Entity

Name Affiliation
Mollnes, Tom Eirik Institute of Clinical Medicine, University of Oslo

Producer

Name Affiliation Abbreviation Role
Mollnes, Tom Eirik Institute of Clinical Medicine, University of Oslo UiO Principal Investigator

Copyright

Copyright (C) 2016 Tom Eirik Mollnes, Institute of Clinical Medicine, UiO

Funding Agency/Sponsor

Name Abbreviation Role Grant
The Research Council of Norway RCN 204874

Data Distributor

Name Affiliation Abbreviation
NSD – Norwegian Centre for Research Data NSD

Version

Date: 2017-05-30

Notes

Original data from Tom Eirik Mollnes, Institute of Clinical Medicine, University of Oslo are documented and prepared, first NSD-version.

Bibliographic Citation

"The Complement System and the CD14/TLR4/MD2 Complex as Targets for Therapy in Sepsis, 2016". Data collected by Tom Eirik Mollnes, Institute of Clinical Medicine, University of Oslo. First NSD edition, Bergen 2017.

List of Keywords

Topic Classification

Time Period Covered

Start End Cycle
2011 2017

Date of Collection

Start End Cycle
2012-01-01 2016-12-31

Country

Norway  (NO)

Unit of Analysis

Other

Kind of Data

Experimental data

Time Method

Cross-sectional survey

Data Collector

Mollnes, Tom Eirik, Institute of Clinical Medicine, University of Oslo  (UiO)

Sampling Procedure

Data is generated mainly as laboratory results of experiments conducted experimentally with whole blood in the laboratory and with tests on pigs. In addition, there is also data from a patient who is published as a casuistic.

Mode of Data Collection

Laboratory observation

Location

Availability Status

Data from "The Complement System and the CD14/TLR4/MD2 Complex as Targets for Therapy in Sepsis, 2016" are made available for everyone when ordered.

Extent of Collection

256 data files; different formats can be made.

Restrictions

Data from "The Complement System and the CD14/TLR4/MD2 Complex as Targets for Therapy in Sepsis, 2016" are made available for everyone when ordered.

Citation Requirement

Users are obliged to refer to producer and distributor of the data by writing the following in forewords or footnotes in eventual publications:
"(Some of) the data applied in the analysis in this publication are based on "The Complement System and the CD14/TLR4/MD2 Complex as Targets for Therapy in Sepsis, 2016". The survey was financed by The Reasearch Council of Norway. The data are provided by Tom Eirik Mollnes, Institute of Clinical Medicine, University of Oslo and prepared and made available by NSD – Norwegian Centre for Research Data. Neither Tom Eirik Mollnes, Institute of Clinical Medicine, University of Oslo, The Research Council of Norway nor NSD are responsible for the analysis/interpretation of the data presented here.

Deposit Requirement

Access to data is given on the condition that NSD gets a PDF-file of eventual reports that are written on the basis of the data. This to ensure best possible information of the use of data we distribute.

Conditions

The order form has to include name, institutional affiliation, project title, information about sources of financing and postal address. A declaration of secrecy has to be signed before delivery of data.

Disclaimer

Neither Tom Erik Mollnes, UiO, The Research Council of Norway nor NSD are responsible for the analysis/interpretation of the data presented here.

Related Publications

Combined inhibition of complement and CD14 attenuates bacteria-induced inflammation in human whole blood more efficiently than antagonizing TLR4-MD2.

Gustavsen, A., Nymo, S., Landsem, A., Christiansen, D., Ryan, L., Husebye, H., Lau, C., Pischke, S.E., Lambris, J.D., Espevik, T. & Mollnes, T.E. (2016) Combined inhibition of complement and CD14 attenuates bacteria-induced inflammation in human whole blood more efficiently than antagonizing TLR4-MD2, in: J Infect Dis 214: p. 140-150.

Human endothelial cell activation by Escherichia coli and Staphylococcus aureus is mediated by TNF and IL-1ß secondarily to activation of C5 and CD14 in whole blood

Nymo, S., Gustavsen, A., Nilsson, P.H., Lau, C., Espevik, T. & Mollnes, T.E. (2016) Human endothelial cell activation by Escherichia coli and Staphylococcus aureus is mediated by TNF and IL-1ß secondarily to activation of C5 and CD14 in whole blood, in: J Immunol 196: p. 2293-2299

Complement factor 5 blockade reduces porcine myocardial infarction size and improves immediate cardiac function

Pischke, S.E., Gustavsen, A., Orrem, H.L., Egge, K.H., Courivaud, F., Fontenelle, H., Despont, A., Bongoni, A.K., Rieben, R., Tønnessen, T.I., Nunn, M.A., Scott, H., Skulstad, H., Barratt-Due, A. & Mollnes T.E. (2017) Complement factor 5 blockade reduces porcine myocardial infarction size and improves immediate cardiac function, in: Basic Res Cardiol. 112:20 (1-14).

Eculizumab before caesarean section in a patient with severe antiphospholipid syndrome - effects on mother and infant

Gustavsen, A., Skattum, L., Bergseth; Lorentzen, B., Fløisand, Y., Bosnes, V., Mollnes, T.E. & Barratt-Due, A. (2017) Eculizumab before caesarean section in a patient with severe antiphospholipid syndrome - effects on mother and infant, in: Medicine 96:e6388 (1-4).

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