Goodman, G. | bioRxiv Science

bioRxiv2026

Inhibition of IL-6 signaling with tocilizumab improves stroke outcomes in aged mice but requires sex-specific dosing

Post-stroke inflammation contributes to poor outcomes in both clinical and experimental studies. Interleukin-6 (IL-6) is a key inflammatory mediator in ischemic stroke, and higher circulating IL-6 levels are associated with greater stroke severity and worse clinical outcomes. Targeting IL-6 signaling therefore represents a potential therapeutic strategy. We tested whether inhibition of IL-6 signaling with the IL-6 receptor (IL-6R) blocking antibody tocilizumab (TCZ) improves recovery after experimental stroke. Aged mice (18-20 months) underwent 60 minutes of middle cerebral artery occlusion. TCZ (20 mg/kg) was administered 5 hours after ischemia onset, and behavioral outcomes were assessed weekly for 5 weeks. Delayed TCZ treatment improved long-term functional recovery in aged male mice but not in aged females. To explore this difference, we measured circulating soluble IL-6R (sIL-6R) levels in mice and patients with ischemic stroke. Females exhibited significantly higher post-stroke sIL-6R levels. Increasing the TCZ dose to 100 mg/kg restored efficacy in aged female mice and improved long-term outcomes. These findings support a role for IL-6R pathway modulation in improving recovery after experimental stroke and suggest that therapeutic response may differ by sex and target availability, potentially related to differences in circulating sIL-6R after ischemic injury.

neuroscience↗

bioRxiv2024

Asymptomatic infection and antibody prevalence to co-occurring avian influenza viruses vary substantially between sympatric seabird species following H5N1 outbreaks

Emerging infectious diseases are of major concern to animal and human health. Recent emergence of high pathogenicity avian influenza virus (HPAIV) (H5N1 clade 2.3.4.4b) led to substantial global mortality across a range of host species. Co-occurring species showed marked differences in mortality, generating an urgent need for better epidemiological understanding within affected populations. We therefore tested for antibodies, indicative of previous exposure and recovery, and for active viral infection in apparently healthy individuals (n=350) across five co-occurring seabird species on the Isle of May, Scotland, during 2023, following H5N1 HPAIV associated mortality in the preceding summer. Antibody prevalence to AIV subtypes varied substantially between species, ranging from 1.1% in European shags (Gulosus aristotelis) (to H5) to 78.7% in black-legged kittiwakes (Rissa tridactyla) (to H16 or both H13 and H16), and between 31-41% for three auk species (H5, H16 or both). At least 20.4% of auks had antibodies to an as yet unidentified subtype, suggesting further subtypes circulating in the population. We found low levels of active, but asymptomatic, AIV infection in individuals (1.6-4.5%), but excluded this as H5N1. Our results emphasise the importance of testing healthy individuals to understand the prevalence of co-circulating AIV subtypes in wild populations, and the potential for future reassortment events which could alter virus behaviour and impact.

ecology↗