Interplay between inflammatory reflex and energetic metabolism in endotoxaemia: A role for haem oxygenase 1?

Inflammation is vital for defence against injury and infection, but excessive inflammation can lead to tissue damage and disease. The central nervous system (CNS) helps regulate immune responses through neuroendocrine pathways, such as the hypothalamic-pituitary-adrenal axis and the anti-inflammatory reflex, which limit systemic inflammation. Immune responses require significant metabolic energy and the liver adapts by increasing glucose production and mobilizing fatty acids. This immune-metabolic coordination is mediated by cytokines and metabolic regulators. This review explores how the anti-inflammatory reflex modulates the interplay between inflammation and metabolism during endotoxaemia, with a focus on the haem oxygenase 1/carbon monoxide (HO1/CO) pathway. Carbon monoxide, a byproduct of HO1 activity, acts as a key signalling molecule that reduces inflammation, supports mitochondrial function and protects tissues. Understanding this pathway provides new insights into potential therapeutic strategies for treating inflammatory and metabolic disorders by targeting neuroimmune-metabolic communication networks.