The exposure to hypoxia is considered to be a stressful stimulus and requires an organism to develop compensatory mechanisms to ensure homeostasis. Acclimation is the most prevalent phenotypic modification that takes place under hypoxia and involves hematological, cardiovascular, renal, and metabolic changes to help the organism to cope with lower O2 levels. At a molecular level, hypoxia evokes highly coordinated cellular responses in order to preserve cell viability. These adaptive responses are orchestrated by the hypoxia-inducible factors (HIF) that regulates the hypoxic response. The mechanisms that take place under continuous hypoxic conditions are different compared to intermittent exposure, mainly because of the distinct signalling pathways activated due to the length and intervals of lower O2 partial pressure. Despite the fact that the adaptive response is aimed at helping the organism to cope with low oxygenation, hypoxia often leads to the development of pathological conditions, most of them involving hypoxia induced-inflammatory processes. If adaptive responses to hypoxia are not effective, individuals may suffer excessive inflammatory responses leading to a number of syndromes, such as acute mountain sickness and cerebral and/or pulmonary edema in the first instance, but also further complications such as bone metabolism alteration, and intestinal, kidney or cardiac disorders, among others, in the long term. In fact, hypoxia amplifies several molecular pathways that are involved in phagocytosis, leukocyte recruitment, and adaptive immunity, meaning that the activation of HIF-1α is necessary to eliminate pathogens. Hypoxia exposure is known to increase cellular oxidative stress leading to the production of reactive oxygen species with deleterious effects on lipids, proteins, and DNA. Moreover, there are studies reporting the inhibitory effects of hyperbaric oxygenation on pro-inflammatory cytokines production, such as IL-1, IL-6, and TNFα, suggesting that this treatment may prevent the damage caused by hypoxia-induced inflammation.

Additionally, hypoxia plays an important role in cancer progression. The hypoxic local environment is especially pronounced in large tumours and it contributes to long-term cellular changes. Oxygen fluctuation is a frequent condition in tumour tissues due to dysfunctional tumour vascularity and heterogenic blood supply, leading to an alteration of the clinical responses to therapy by influencing tumour growth, ability to metastasize, and resistance to cell death. In hypoxic tumour tissue, not only cancer cells but also the tumour microenvironment, including immune cells, stromal cells, extracellular matrix cytokines and other mediators, is affected by hypoxia-inducible change.

In summary, hypoxia exposure can induce several pathological conditions due to the resulting excessive inflammatory response. Therefore, this Special Issue invites investigators to contribute with original research and review articles to expand the understanding of hypoxia, a condition that may induce local or systemic inflammatory processes that can alter the homeostasis of the organism in a severe manner.

Potential topics include but are not limited to the following:

• Hypoxia-induced inflammation
• Hypoxia signalling and innate immunity
• Hypoxia and adaptive immunity
• Hypoxia and its associated pathological conditions
• Hypoxia and organic failures
• Obstructive Sleep Apnea and inflammation
• Bone metabolism disorders related to hypoxia exposition
• Hypoxia and cancer progression and metastases
• Hypoxia and infectious diseases
• Oxidative stress induced by hypoxia
• Cerebral hypoxia