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Interleukin 6 Is Elevated in Andean Highlanders with Chronic Mountain Sickness
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A2365 - Interleukin 6 Is Elevated in Andean Highlanders with Chronic Mountain Sickness
Author Block: E. Heinrich1, C. Anza-Ramirez2, J. Macarlupu2, N. Corante2, G. Vizcardo-Galindo2, M. Djokic1, F. C. Villafuerte2, F. L. Powell1, T. S. Simonson1; 1Medicine, University of California, San Diego, La Jolla, CA, United States, 2Laboratorio de Fisiologia, Universidad Peruana Cayetano Heredia, Lima, Peru.
Rationale: Chronic Mountain Sickness (CMS) is a clinical syndrome found in long-term high-altitude residents and is mainly characterized by excessive erythrocytosis (EE) and frequently sever hypoxemia. Reduced ventilation, poor sleep quality, and a post-menopausal state in women are associated with CMS. We predict that hypoxia-induced chronic inflammation may also play a role in the development of excessive erythrocytosis and that interleukin-6 (IL-6) may be a key player due to its role in hematopoiesis and its upregulation in visitors to high altitude.
Methods: Residents of Cerro de Pasco, Peru (CDP; 4,300 m) with and without excessive erythrocytosis (Hb ≥ 19 g/dL in women, and Hb ≥ 21 g/dL in men) were included in this study: 46 women (4 with EE; age: 40.0 ± 13.5 years; BMI: 27.7 ± 4.4) and 51 men (20 with EE; age: 42.2 ± 13.2 years; BMI: 25.4 ± 4.4). IL-6 was also measured in serum collected from 18 sea-level residents (6 women, 12 men; age: 28.6 ± 4.1; BMI: 24.3 ± 2.6) at sea level and daily over 3 days at 3,800m (White Mountain Research Station; Bishop, CA). DNA and plasma were isolated from venous blood samples and IL-6 protein levels were measured in plasma via ELISA.
Results: Plasma IL-6 was significantly higher in Andean men with EE (healthy: 1.0 ± 0.4 pg/mL, EE: 2.5 ± 2.0 pg/mL; p = 0.02). IL-6 also increased in sea-level participants from 1.2 ± 0.6 to 2.3 ± 0.7 pg/mL (p = 0.01) after one day at 3,800 m.
Conclusions: IL-6 increases during hypoxic exposure in healthy sea level residents at high altitude. Andean highlanders with EE also had elevated levels of IL-6 but healthy Andean highlanders had IL-6 levels similar to sea level residents. Elevated IL-6 in EE could result from increased IL-6 release by monocytes and vascular cells in response to more severe hypoxemia in this group, differences in the responsiveness of their inflammatory pathways, or increased blood vessel sheer stress imposed by increased blood viscosity in EE subjects. In any case, elevated IL-6 could exacerbate CMS by further stimulating hematopoiesis.
Author Block: E. Heinrich1, C. Anza-Ramirez2, J. Macarlupu2, N. Corante2, G. Vizcardo-Galindo2, M. Djokic1, F. C. Villafuerte2, F. L. Powell1, T. S. Simonson1; 1Medicine, University of California, San Diego, La Jolla, CA, United States, 2Laboratorio de Fisiologia, Universidad Peruana Cayetano Heredia, Lima, Peru.
Rationale: Chronic Mountain Sickness (CMS) is a clinical syndrome found in long-term high-altitude residents and is mainly characterized by excessive erythrocytosis (EE) and frequently sever hypoxemia. Reduced ventilation, poor sleep quality, and a post-menopausal state in women are associated with CMS. We predict that hypoxia-induced chronic inflammation may also play a role in the development of excessive erythrocytosis and that interleukin-6 (IL-6) may be a key player due to its role in hematopoiesis and its upregulation in visitors to high altitude.
Methods: Residents of Cerro de Pasco, Peru (CDP; 4,300 m) with and without excessive erythrocytosis (Hb ≥ 19 g/dL in women, and Hb ≥ 21 g/dL in men) were included in this study: 46 women (4 with EE; age: 40.0 ± 13.5 years; BMI: 27.7 ± 4.4) and 51 men (20 with EE; age: 42.2 ± 13.2 years; BMI: 25.4 ± 4.4). IL-6 was also measured in serum collected from 18 sea-level residents (6 women, 12 men; age: 28.6 ± 4.1; BMI: 24.3 ± 2.6) at sea level and daily over 3 days at 3,800m (White Mountain Research Station; Bishop, CA). DNA and plasma were isolated from venous blood samples and IL-6 protein levels were measured in plasma via ELISA.
Results: Plasma IL-6 was significantly higher in Andean men with EE (healthy: 1.0 ± 0.4 pg/mL, EE: 2.5 ± 2.0 pg/mL; p = 0.02). IL-6 also increased in sea-level participants from 1.2 ± 0.6 to 2.3 ± 0.7 pg/mL (p = 0.01) after one day at 3,800 m.
Conclusions: IL-6 increases during hypoxic exposure in healthy sea level residents at high altitude. Andean highlanders with EE also had elevated levels of IL-6 but healthy Andean highlanders had IL-6 levels similar to sea level residents. Elevated IL-6 in EE could result from increased IL-6 release by monocytes and vascular cells in response to more severe hypoxemia in this group, differences in the responsiveness of their inflammatory pathways, or increased blood vessel sheer stress imposed by increased blood viscosity in EE subjects. In any case, elevated IL-6 could exacerbate CMS by further stimulating hematopoiesis.
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