# Cationic Antimicrobial Copolymers Reveal Immunomodulatory Properties in Lipopolysaccharide Stimulated Macrophages in Vitro

## TL;DR

Scientists found that certain antimicrobial copolymers can reduce inflammation in immune cells, suggesting they could help fight infections and prevent sepsis.

## Contribution

The study reveals that specific cationic antimicrobial copolymers have anti-inflammatory and antimicrobial dual-action properties.

## Key findings

- Two diblock copolymers suppressed the NF-κB pathway and reduced IL-6 production in LPS-activated macrophages.
- The cationic-apolar copolymer showed strong antimicrobial activity against P. aeruginosa.
- These copolymers may help prevent sepsis by reducing inflammation at the infection site.

## Abstract

Antimicrobial polymers, which have emerged as a promising
alternative
to antibiotics in the fight against antimicrobial resistance, are
based on the design of cationic host defense peptides (CHDPs). Being
part of the mammalian innate immune system, CHDPs possess both antimicrobial
and immunoregulatory effects to manage bacterial infections. However,
the immunomodulatory effects of antimicrobial polymers remain largely
unexplored. Within this work, a library of 15 copolymers was synthesized
by reversible addition–fragmentation chain transfer (RAFT)
polymerization and their abilities to modulate pro-inflammatory pathways
in lipopolysaccharide (LPS)-activated murine and human macrophages
were investigated. We found that two diblock copolymers with cationic
units copolymerized with either apolar or hydrophilic comonomers appeared
to have anti-inflammatory activity through suppression of the activation
of the nuclear factor kappa-light-chain enhancer of the activated
B cell (NF-κB) signaling pathway, scavenging of reactive oxygen
species, and reduced production of the pro-inflammatory cytokine interleukin-6
(IL-6). Furthermore, the cationic-apolar copolymer exhibits significant
antimicrobial activity against P. aeruginosa. Thus, this promising copolymer holds potential as a dual-action
therapeutic, effectively combating bacterial infections while curbing
prolonged inflammation and thereby preventing sepsis at the site of
infection.