Fig. 3
From: Immunomodulation after ischemic stroke: potential mechanisms and implications for therapy
Ischemic stroke induces systemic immunosuppression mediated by several factors. These are: (1) overactivation of the sympathetic nervous system (SNS) results in secretion of catecholamines, which act on β-adrenergic receptors (ARβ2), dopaminergic receptors (dopamine receptor D2, DRD2), acetylcholine, and hepatic invariant natural killer T-cell (iNKT) stimulation; (2) activation of the hypothalamic-pituitary-adrenal (HPA) axis results in excessive glucocorticoid (GC) secretion, which acts on T cells to reduce interferon (IFN)-γ production, inducing apoptotic cell death and promoting interleukin (IL)-10 secretion through regulatory T cells (T reg ); (3) parasympathetic nervous system (PNS) stimulation activates the cholinergic anti-inflammatory pathway, driven by the efferent vagus nerve at nAChRα7 receptors expressed in alveolar macrophages (Mθ) and lung epithelial cells, reducing tumor necrosis factor (TNF)-α and interleukin (IL)-1β; and (4) damage-associated molecular patterns (DAMPs) are released by cells undergoing non-apoptotic death or by immune system cells, characterized by reduced major histocompatibility complex (MHC)-II expression, decreased cytokine production upon stimulation, and T cell dysfunction. This contributes to the overall immunosuppressive state after stroke, which is the main explanation for post-stroke susceptibility to infection. Blue arrows represent the systemic effects of stroke. Green lines represent possible therapeutic targets to prevent systemic immunosuppression and stroke-associated pneumonia. AD adrenalin, NR noradrenaline, RAGE receptor for advanced glycation end-products, TLR toll-like receptor