Hypoxia-Induced Inflammatory Chemokines in Subjects with a History of High-Altitude Pulmonary Edema

Abstract

High altitude hypoxia is known to induce an inflammatory response in immune cells. Hypoxia induced inflammatory chemokines may contribute to the development of high altitude pulmonary edema (HAPE) by causing damage to the lung endothelial cells and thereby capillary leakage. In the present study, we were interested to know whether chronic inflammation may contribute to HAPE susceptibility. We examined the serum levels of macrophage inflammatory protein-1α (MIP-1α), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 in group (1) HAPE Susceptible subjects (n = 20) who had past history of HAPE and group (2) Control (n = 18) consist of subjects who had stayed at high altitude for 2 years without any history of HAPE. The data obtained confirmed that circulating MCP-1, MIP-1α were significantly upregulated in HAPE-S individuals as compared to the controls suggestive of chronic inflammation. However, it is not certain whether chronic inflammation is cause or consequence of previous episode of HAPE. The moderate systemic increase of these inflammatory markers may reflect considerable local inflammation. The existence of enhanced level of inflammatory chemokines found in this study support the hypothesis that subjects with past history of HAPE have higher baseline chronic inflammation which may contribute to HAPE susceptibility.

Subclinical pulmonary dysfunction contributes to high altitude pulmonary edema susceptibility in healthy non-mountaineers

“…Since then additional studies have also confirmed associations between reduced FVC and a variety of non-pulmonary diseases including stroke, diabetes, hypertension, amongst others 28 . The chronic systemic inflammation 29 and chronic hypoxia mediated vascular remodeling 6 , 7 observed in our previous studies on non mountaineer HAPE-S can lead to a combination of small airway disease and reduced pulmonary vascular bed capacity, which may not manifest at sea level but prevent adequate compensatory increase in ventilation and perfusion, leading to HAPE. In support, the restrictive pattern shown by HAPE-S2 and asthma pattern 16 shown by HAPE-S1 in our study has been strongly associated with presence of small airway or vascular disease in a large observational cross-sectional and longitudinal study 30 .…”

Endogenous Ligands of Toll Like Receptors: A Danger Signal to the Brain Memory at High Altitude

“…These endogenous ligands up-regulated during high altitude sojourn. Finally, they bound to their receptors such as TLR-4, which in downstream signaling cascade up-regulate proin lammatory mediators like TNF-alpha and interlukin-1 beta and proin lammatory chemokines by activation of transcription factor NF-kB [5,6]. The increased level of TNF-alpha upregulate apoptosis of the brain cells in different regions such as Hippocampus and prefrontal cortex.…”

Chemokines in High Altitude Pulmonary Edema

“…We read the article titled ''Hypoxia-induced inflammatory chemokines in subjects with a history of high-altitude pulmonary edema'' by Mishra et al [1] with profound interest. Indeed hypoxia exposure whether, in vitro or in vivo, is associated with rise in inflammatory markers.…”