The potential of IFN-λ, IL-32γ, IL-6, and IL-22 as safeguards against human viruses: a systematic review and a meta-analysis.

Many studies have investigated the antiviral activity of cytokines, including interleukin-6 (IL-6), interleukin-22 (IL-22), interleukin-32 gamma (IL-32γ), and interferon-lambda (IFN-λ) in diverse populations. This study aims to evaluate the role of these cytokines in inhibition of various human and animal viruses when administered exogenously. A comprehensive meta-analysis and systematic review were conducted on all the relevant studies from three databases. Standard mean differences (SMDs) of overall viral inhibition were used to generate the difference in the antiviral efficacy of these cytokines between control and experimental groups. A total of 4,618 abstracts for IL-6, 3,517 abstracts for IL-22, 2,160 abstracts for IL-32γ, and 1,026 abstracts for IFN-λ were identified, and 7, 4, 8, and 35 studies were included, respectively, for each cytokine. IFN-λ (SMD = 0.9540; 95% CI: 0.69-0.22) and IL-32γ (SMD = 0.459; 95% CI: 0.02-0.90) showed the highest influence followed by IL-6 (SMD = 0.456; CI: -0.04-0.95) and IL-22 (SMD = 0.244; 95% CI: -0.33-0.81). None of the cytokines represented heterogeneity (tau² > 0), but only IFN-λ indicated the funnel plot asymmetry (p = 0.0097). Results also indicated that IFN-λ and IL-32γ are more potent antivirals than IL-6 and IL-22. The collective findings of this study emphasize that exogenously administered pro-inflammatory cytokines, specifically IFN-λ and IL-32, exhibit a significant antiviral activity, thereby underscoring them as potent antiviral agents. Nonetheless, additional research is required to ascertain their clinical utility and potential for integration into combinatorial therapeutic regimens against viral infections.

Navigating the brain: the role of exosomal shuttles in precision therapeutics.

Brain diseases have become one of the leading roots of mortality and disability worldwide, contributing a significant part of the disease burden on healthcare systems. The blood-brain barrier (BBB) is a primary physical and biological obstacle that allows only small molecules to pass through it. Its selective permeability is a significant challenge in delivering therapeutics into the brain for treating brain dysfunction. It is estimated that only 2% of the new central nervous system (CNS) therapeutic compounds can cross the BBB and achieve their therapeutic targets. Scientists are exploring various approaches to develop effective cargo delivery vehicles to promote better therapeutics targeting the brain with minimal off-target side effects. Despite different synthetic carriers, one of the natural brain cargo delivery systems, "exosomes," are now employed to transport drugs through the BBB. Exosomes are naturally occurring small extracellular vesicles (EVs) with unique advantages as a therapeutic delivery system for treating brain disorders. They have beneficial innate aspects of biocompatibility, higher stability, ability to cross BBB, low cytotoxicity, low immunogenicity, homing potential, targeted delivery, and reducing off-site target effects. In this review, we will discuss the limitations of synthetic carriers and the utilization of naturally occurring exosomes as brain-targeted cargo delivery vehicles and highlight the methods for modifying exosome surfaces and drug loading into exosomes. We will also enlist neurodegenerative disorders targeted with genetically modified exosomes for their treatment.