Hyperbaric oxygen therapy modulates immune effector responses and reshapes peripheral immune tolerance: a narrative review

Hyperbaric oxygen therapy (HBOT) refers to an intervention in which patients inhale near-100% oxygen at pressures exceeding 1 atmosphere absolute to increase plasma and tissue oxygen partial pressure. HBOT has been applied clinically across a broad range of conditions, including infections, inflammation, hypoxia-related injury, and malignancies. However, its immunological effects are often reduced to a binary notion of "immune enhancement" or "immunosuppression". Moreover, substantial heterogeneity in treatment parameters and immune endpoints across studies has limited the development of a unified interpretive framework centered on peripheral immune tolerance (PIT). Following the PRISMA 2020 reporting framework, we standardized the presentation of the search and selection process. PubMed, Embase, Web of Science, the Cochrane Library, and Scopus were searched from database inception to November 15, 2025. Two reviewers independently performed study screening and data extraction. Ultimately, 39 relevant articles were included, and a mechanism-oriented qualitative narrative synthesis was conducted along the axes of oxygen tension, immunometabolism, and PIT. Across the included studies, in models of autoimmune and chronic inflammatory disease, HBOT was commonly associated with expansion of regulatory T cells and suppression of T helper 17-related inflammatory pathways, accompanied by a homeostatic recalibration of peripheral tolerance thresholds and improved tissue inflammatory outcomes. Under infectious and hyperinflammatory conditions, pro-inflammatory transcriptional signatures and cytokine responses were attenuated, markers of oxidative damage were reduced, while neutrophil directional bactericidal capacity was enhanced, suggesting synergy with certain antimicrobial therapies. In hypoxic tumor microenvironments, antigen presentation was improved, cytotoxic T-cell infiltration increased, and immunosuppressive myeloid components decreased, collectively indicating potential additive or synergistic benefits with immunotherapy. In summary, we propose an integrated framework in which upstream oxygen tension sensing drives intermediate immunometabolic remodeling, culminating in downstream reprogramming of immune cell lineages and functional states. This framework provides a testable theoretical basis for explaining the context-dependent immunological effects of HBOT across diseases and for guiding prospective study designs incorporating composite immune endpoints and therapeutic windows.