A group of scientists have developed a targeted delivery platform that can induce anti-inflammatory cytokine expression in mouse lungs, which helps restrict tissue damage from respiratory infections without triggering systemic side effects. Full details are published in Science Immunology in a paper titled “Gene delivery of immunomodulatory cytokines to the lung preserves respiratory function during inflammatory challenge.”
The study was led by scientists in the pathology department at the University of Cambridge, who collaborated to create a gene delivery system that expresses anti-inflammatory cytokines in the lung, restoring local immune homeostasis without systemic effects. Utilizing an adeno-associated virus cargo system (AAV6.2-CC10), they successfully induced production of interleukin-2 (IL-2), IL-1 receptor antagonist (IL-1RA), and IL-10 in situ in the lung microenvironment, with no detectable expression in the peripheral immune system.
Developers suggest this innovative approach could pave the way for new therapeutics aimed at controlling inflammation in viral infections, which have been linked to increased mortality rates in SARS-CoV-2 and influenza cases. Prolonged inflammation heightens the risk of secondary bacterial and fungal infections. This method effectively harnesses the therapeutic potential of immunomodulatory cytokines, which have historically faced challenges due to short half-lives and multiorgan effects. The tool demonstrates sustained and localized expression, as evidenced by prolonged production of the tested cytokines restricted to the lungs over weeks.
The paper details how the scientists characterized their method, demonstrating specific expression in lung epithelial cells without off-target accumulation. Their findings indicate that while IL-2 expression did not significantly benefit infection outcomes, IL-1RA and IL-10 reduced tissue damage and improved recovery. Furthermore, delivering either individual cytokines or a combination protected mice from influenza-associated aspergillosis, resulting in improved health outcomes.
Future experiments with human cell culture systems could set the stage for preclinical testing, although limitations exist. The scientists noted that repeated administration of AAV vectors may lead to neutralizing antibodies that hinder uptake in subsequent treatments. Additionally, while effective in mouse models, the utility of this cargo in patient settings requires further investigation.
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