Damage-Associated Molecular Patterns as Key Modulators of Immune Responses in High-Altitude Hypoxia

High altitude hypoxia disrupts the homeostasis and functioning of different organs including the gut, brain and lungs. This may be due to many factors including release of proinflammatory cytokines, chemokines and damage associated molecular patterns (DAMPs). Systemic hypoxia may lead to cellular damage and cell death, such as apoptosis, necrosis and pyroptosis, which may release several DAMP molecules that can bind with innate immune receptors and can activate an immune response. This may result in life threatening conditions like high altitude pulmonary edema (HAPE), high altitude cerebral edema (HACE) and gastrointestinal permeability. The emerging research on animal and human studies points towards the pathobiological role of DAMPs in hypoxic injury in multiple organs. In this review, we have included studies on the role of DAMPs in hypobaric hypoxia published between the years 1994 to 2026 using databases such as PubMed and Google scholar. The present review summarizes the DAMPs released during high altitude hypoxia exposure and elucidates their molecular mechanism in inducing sterile inflammation. This may be beneficial in discovering new therapeutic strategies and drug targets to mitigate the hypobaric hypoxia induced tissue damage and severe complications in multiple organs.