NDLI: TLR4 inhibition impairs bacterial clearance in a therapeutic setting in murine abdominal sepsis

Content Provider	Springer Nature Link
Author	Lieshout, Miriam H. P. Poll, Tom Veer, Cornelis
Copyright Year	2014
Abstract	To investigate the therapeutic effect of E5564 (a clinically used TLR4 inhibitor) in murine abdominal sepsis elicited by intraperitoneal infection with a highly virulent Escherichia coli in the context of concurrent antibiotic therapy.Mice were infected with different doses (~2 × 104–2 × 106 CFU) of E. coli O18:K1 and treated after 8 h with ceftriaxone 20 mg/kg i.p. combined with either E5564 10 mg/kg i.v. or vehicle. For survival studies this treatment was repeated every 12 h. Bacterial loads and inflammatory parameters were determined after 20 h in peritoneal lavage fluid, blood, liver and lung tissue. Plasma creatinin, AST, ALT and LDH were determined to assess organ injury.E5564 impaired bacterial clearance under the antibiotic regime after infection with a low dose E. coli (1.7 × 104 CFU) while renal function was slightly preserved. No differences were observed in bacterial load and organ damage after infection with a tenfold higher (1.7 × 105 E. coli) bacterial dose. While treatment with E5564 slightly attenuated inflammatory markers provoked by the sublethal doses of 104–105 E. coli under the antibiotic regime, it did not affect lethality evoked by infection with 1.7 × 106 E. coli.The impact of TLR4 inhibition during abdominal sepsis by virulent E. coli bacteria is only beneficial at low infection grade at cost of bactericidal activity.
Starting Page	927
Ending Page	933
Page Count	7
File Format	PDF
ISSN	10233830
Journal	Inflammation Research
Volume Number	63
Issue Number	11
e-ISSN	1420908X
Language	English
Publisher	Springer Basel
Publisher Date	2014-08-15
Publisher Place	Basel
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	TLR4 Abdominal sepsis Anti-TLR4 therapy E5564 Immunology Pharmacology/Toxicology Rheumatology Allergology Dermatology Neurology
Content Type	Text
Resource Type	Article
Subject	Pharmacology Immunology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

E5564 (Eritoran) inhibits lipopolysaccharide-induced cytokine production in human blood monocytes

Bacterial Infection

Macrophages as Targets of Anti-Inflammatory Therapy

Rac1 regulates bacterial toxin-induced thrombin generation

TLR4 polymorphisms and disease susceptibility

Bacterial Infection and Host Reaction

Therapeutic potential of targeting inflammation

Symposium 3: Anti-Inflammatory Mechanisms

Metalloproteinases regulate CD40L shedding from platelets and pulmonary recruitment of neutrophils in abdominal sepsis

TLR4 inhibition impairs bacterial clearance in a therapeutic setting in murine abdominal sepsis

Similar Documents

E5564 (Eritoran) inhibits lipopolysaccharide-induced cytokine production in human blood monocytes

Bacterial Infection

Macrophages as Targets of Anti-Inflammatory Therapy

Rac1 regulates bacterial toxin-induced thrombin generation

TLR4 polymorphisms and disease susceptibility

Bacterial Infection and Host Reaction

Therapeutic potential of targeting inflammation

Symposium 3: Anti-Inflammatory Mechanisms

Metalloproteinases regulate CD40L shedding from platelets and pulmonary recruitment of neutrophils in abdominal sepsis

TLR4 inhibition impairs bacterial clearance in a therapeutic setting in murine abdominal sepsis