The Neuroimmune Mechanisms Linking Smoking and Infection to Atherosclerosis: Chronic vs. Surge

The pathogenesis of atherosclerosis has progressively shifted from a lipid-centric model to one that recognizes inflammation as the central driver. Smoking is a well-established chronic risk factor, whereas acute infections are increasingly recognized as transient triggers of acute cardiovascular events. This review synthesizes the distinct yet overlapping mechanisms by which chronic smoking and acute infections contribute to atherogenesis and plaque destabilization within an integrated neuroimmune framework. This narrative review was developed using AI-assisted literature search tools (ChatGPT, OpenAI; Claude, Anthropic) to identify relevant publications from 1990 to 2025. All references were independently verified using PubMed and original source links. Selection prioritized mechanistic studies addressing inflammatory pathways, endothelial dysfunction, and immune modulation. Smoking promotes atherogenesis through sustained endothelial injury, lipoprotein oxidation, chronic sympathetic activation, and hematopoietic reprogramming, favoring proinflammatory monocyte mobilization. Infections elicit acute cytokine surges, sympathetic-mediated macrophage activation, and prothrombotic cascades that destabilize preexisting plaques. Smoking contributes to plaque initiation and growth, whereas infections primarily act as event triggers. Atherosclerosis emerges from chronic and episodic inflammatory processes with distinct temporal profiles. Smoking is a continuous driver of plaque formation, whereas acute infections promote plaque destabilization. Future research should examine their interplay, particularly in smokers exposed to recurrent or low-grade infectious states.