Immunomodulatory therapies in bacterial community-acquired pneumonia: Current evidence and future directions

Community-acquired pneumonia remains a leading cause of morbidity and mortality worldwide, accounting for more than two million deaths annually. While most patients successfully clear pulmonary infection through an effective host immune response, a subset progress to severe disease characterised by dysregulated and excessive inflammation. This maladaptive immune response drives subsequent organ dysfunction and mortality, prompting increasing interest in immunomodulatory therapies as adjunctive treatments.

This article aims to describe the key immunomodulatory strategies investigated for the management of bacterial community-acquired pneumonia, summarise the evidence for their efficacy and limitations, and highlight potential future therapeutic approaches.

We conducted a comprehensive literature search of Medline, Embase, Web of Science, Scopus and Global Health, using search terms related to pneumonia and immunomodulatory intervention from database inception to December 8^th, 2025.

While a broad range of immunomodulatory strategies has been investigated in bacterial community-acquired pneumonia, few have been shown to be reliably beneficial. Corticosteroids are the most extensively studied agents and have been associated with clinically relevant outcomes in selected patient populations, supporting guideline recommendations for their use in severe community-acquired pneumonia. Targeted inhibition of inflammatory cytokines and downstream signalling pathways has been explored to a lesser degree, with limited evidence supporting its use in bacterial community-acquired pneumonia. Other approaches, including passive immunotherapy and immune stimulation, have been investigated, but current evidence supporting their routine use remains inconclusive.

Immunomodulation represents an important adjunctive therapeutic strategy in bacterial community-acquired pneumonia. Although progress has been made, particularly with corticosteroids, evidence remains incomplete. Further high-quality research is required to better define patient selection, optimal timing, and the clinical impact of immunomodulatory therapies.