Interleukin-1 regulates myeloid cell trafficking and cerebral blood flow following intracerebral haemorrhage

Barrington, Jack and Rivers-Auty, Jack and Strangward, Patrick and Tamburrano, Sabrina and Lénárt, Nikolett and Swanton, Tessa and Lemarchand, Eloise and Parry-Jones, Adrian R. and Dénes, Ádám and Brough, David and Allan, Stuart M. (2025) Interleukin-1 regulates myeloid cell trafficking and cerebral blood flow following intracerebral haemorrhage. DISEASE MODELS & MECHANISMS, 18 (10). No. 052306. ISSN 1754-8403

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Abstract

Intracerebral haemorrhage (ICH) is a devastating stroke subtype lacking effective therapies. Understanding key pathological processes related to acute brain damage will help deliver better outcomes for ICH. Herein, we provide evidence that myeloid cell trafficking to the parenchyma is a conserved feature of ICH in clinical and experimental settings. Consistent with others, we show that monocytes contribute to acute brain damage following collagenase-induced murine ICH. Using RNA sequencing, we identified the pro-inflammatory cytokine interleukin-1 (IL-1) as a potential upstream regulator of the acute inflammatory response, with histological data pinpointing mononuclear phagocytes as the principal cellular source of IL-1 in patient and animal tissue. In agreement, inhibition of IL-1 receptor 1 (IL-1R1) with IL-1 receptor antagonist reduced recruitment of myeloid cells. However, IL-1R1 inhibition also worsened neuromotor outcomes and reduced cerebral blood flow to the affected hemisphere. Thus, we reveal dichotomous actions of IL-1-dependent inflammation following brain haemorrhage. Although IL-1 regulates myeloid cell trafficking, it also appears to regulate cerebral blood flow. Therefore, further investigation into the consequences of IL-1 signalling following brain haemorrhage is required to clarify future therapeutic options.

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