Related Experiment Video
Updated: Feb 6, 2026

A Controlled Mouse Model for Neonatal Polymicrobial Sepsis
Published on: January 27, 2019
Neurokinin-1 Receptor Deficiency Improves Survival in Murine Polymicrobial Sepsis Through Multiple Mechanisms in Aged
Juan R Mella1, Arthur F Stucchi, Elizabeth R Duffy
1Boston University School of Medicine, Boston, Massachusetts.
Objective:
Substance P (SP) is a neuropeptide that contributes to a proinflammatory state by binding to the neurokinin 1 receptor (NK-1R). Limiting this interaction has been shown to attenuate the acute inflammation. Our hypothesis was that NK-1R activation would contribute to the morbidity and mortality of sepsis in a model using mice genetically deficient in the NK-1R.
Methods:
To investigate the role of the SP/NK-1R axis in a murine model of sepsis, cecal ligation and puncture (CLP) in NK-1R deficient and wild type (WT) aged mice was performed. Acute inflammation was assessed by measuring circulating cytokines and clinical parameters.
Results:
Deletion of the NK-1R results in improved survival following CLP (NK-1R knockout mice survival = 100% vs. WT = 14%). A reduction in the inflammatory cytokines interleukin (IL) 6, macrophage inflammatory peptide 2, and IL-1 receptor antagonist, improved hemodynamic parameters, and increased neutrophilia were present in the NK-1R-deficient mice after CLP compared with WT mice.
Conclusions:
These data confirm the hypothesis that eliminating the SP/NK-1R interaction in a highly lethal murine model of sepsis leads to decreased morbidity and mortality through multiple mechanisms.
Related Concept Videos
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
SN1 Reaction: Mechanism
Firstly, the haloalkane ionizes to generate a carbocation intermediate and a halide ion. This heterolytic cleavage is highly endothermic with large activation energy. The ionization of the substrate, facilitated by a...
Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Transducer Mechanism: G Protein–Coupled Receptors
GPCRs are also called heptahelical,...
Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism

