Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome

Anub Mathew Thomas1, Camilla Schjalm1, Per H Nilsson1,2

  • 1Department of Immunology, Oslo University Hospital and K.G. Jebsen IRC, University of Oslo, Oslo, Norway.

Neonatology
|February 28, 2018
PubMed
Abstract

Insights

Combined inhibition of complement C5 and CD14 significantly reduces inflammation in a piglet model of meconium aspiration syndrome (MAS). This synergistic approach offers a promising new therapeutic strategy for MAS, a severe neonatal lung condition.

Area of Science:

  • Neonatal Medicine
  • Immunology
  • Pulmonology

Background:

  • Meconium aspiration syndrome (MAS) causes severe neonatal lung injury and systemic inflammation.
  • Previous studies showed complement activation and cytokine release in MAS, with inflammation dependent on complement and Toll-like receptors.
  • MAS can lead to a systemic inflammatory response, impacting newborn health.

Purpose of the Study:

  • To evaluate the efficacy of combined C5 complement inhibition and CD14 blockade.
  • To assess the impact on systemic inflammation in a piglet model of meconium aspiration syndrome (MAS).

Main Methods:

  • Thirty piglets were randomized into a treatment group (C5 inhibitor SOBI002 + anti-CD14) and a control group.
  • MAS was induced via intratracheal meconium instillation, with a 5-hour observation period.
  • Complement, cytokines (IL-1β, IL-6), and myeloperoxidase (MPO) were measured.

Main Results:

  • Combined C5 and CD14 inhibition effectively reduced IL-1β by 60% and IL-6 by 44%.
  • Myeloperoxidase (MPO) activity in bronchoalveolar fluid decreased by 42% with combined treatment.
  • Ex vivo studies showed synergistic effects, with minimal benefit from single inhibition.

Conclusions:

  • Combined inhibition of C5 and CD14 effectively attenuates meconium-induced inflammation in vivo.
  • This synergistic approach presents a potential future therapeutic regimen for meconium aspiration syndrome (MAS).
  • The study highlights the crucial cross-talk between C5 and CD14 in MAS pathogenesis.

Related Concept Videos

Transcription Attenuation in Prokaryotes02:42

Transcription Attenuation in Prokaryotes

Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure.  Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
18.6K
Inflammation01:38

Inflammation

Overview
62.4K
Feedback Inhibition00:46

Feedback Inhibition

Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!
57.3K
Pharmacodynamic Models: Link Model and Systems Pharmacodynamic Model01:14

Pharmacodynamic Models: Link Model and Systems Pharmacodynamic Model

The link model is a fundamental pharmacokinetic-pharmacodynamic (PK–PD) approach to account for delayed drug responses when the observed effect does not immediately correlate with the drug's plasma concentration peak. This delay is mathematically addressed by introducing an effect compartment concentration, Ce, which is kinetically linked to the plasma concentration, Cp, via a first-order rate constant, ke0. The linkage allows for a more accurate prediction of drug effects over time. A...
2
Enzyme Inhibition01:30

Enzyme Inhibition

Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
92.8K