Objective:

To systematically summarize key cellular and molecular immune mechanisms underlying the development and progression of stroke-associated pneumonia (SAP) and to critically discuss current pharmacological strategies targeting the immune system for preventing or treating SAP.

Approach:

• Search Strategy: Systematic search of PubMed, Scopus, Web of Science, and Embase for studies on immune mechanisms and immunomodulatory therapies for SAP, following PRISMA guidelines.
• Eligibility Criteria: Included studies focused on experimental stroke models evaluating pulmonary inflammation or lung infection, immune mechanisms related to pneumonia post-stroke, and therapeutic approaches targeting the immune system.
• Data Extraction: Data was independently extracted and verified by researchers from the included studies, focusing on various categories such as author, year of publication, animal species, model, and primary outcomes.

Key Findings:

• Stroke severity disrupts immune homeostasis, leading to SAP through a multi-layered network.
• Systemic immunosuppression is primarily mediated by sympathetic nervous system overactivation, causing splenic atrophy and lymphocyte apoptosis.
• Sustained activation of the cholinergic anti-inflammatory pathway may impair pulmonary antimicrobial defense.
• Disruption of the gut-lung axis and local pulmonary alterations are implicated in SAP development.
• Interventions targeting immune mechanisms, such as iNKT cell activators, show promise in preclinical models.

Interpretation:

The review synthesizes the mechanistic basis of SAP and identifies emerging immunomodulatory interventions, emphasizing the need for further validation of these strategies in clinical settings.

Limitations:

• The review protocol was not prospectively registered, affecting transparency.
• Most immunomodulatory strategies discussed remain experimental and require further validation for clinical application.

Conclusion:

The review highlights the urgent need for a systematic integration of existing evidence and the development of innovative strategies against SAP.