Relationship between Baseline Inflammation and Peak Erythropoietin Levels in People Undergoing Carbon Monoxide Inhalation and Hot Water Immersion
| dc.contributor.advisor | Andrew Lovering | |
| dc.contributor.advisor | Trond Jacobsen | |
| dc.contributor.author | Weiser, Natasha | |
| dc.date.accessioned | 2023-09-19T22:56:17Z | |
| dc.date.available | 2023-09-19T22:56:17Z | |
| dc.date.issued | 2023-03 | |
| dc.description | 35 pages | en_US |
| dc.description.abstract | Erythropoietin (EPO) is a hormone produced by the kidneys that is responsible for stimulating red blood cell (RBC) production. The stimulus for EPO production is a reduction in oxygen delivery to the kidneys, which can occur by reducing either the rate of blood flow or the oxygen content of the blood being delivered to the kidneys. However, EPO is not the only protein that can regulate RBCs. High levels of circulating inflammatory proteins can negatively impact RBC mass, and one of the pathways by which this can occur is by inhibiting EPO production. Recently, carbon monoxide (CO) inhalation and heat have been used as ways to reduce renal oxygen delivery, yet no studies have examined these treatments in combination nor the effects of inflammation on the EPO response in humans. The purpose of this study was twofold: 1) to determine whether combining CO inhalation and heat via hot water immersion has an additive effect on circulating EPO concentration, and 2) to examine the association between baseline inflammatory protein concentrations and EPO concentrations. It was hypothesized that 1) CO and heat will have an additive effect on circulating EPO concentrations, and 2) higher baseline levels of circulating inflammation will result in reduced EPO concentration in response to heat and CO stimuli. By inducing a hypoxic response through the interventions of CO inhalation, hot water immersion, and combined CO inhalation and heat, the mechanism(s) by which EPO is released can be better understood. Research on this topic also has important implications in treating high circulating inflammation in chronic diseases and female athletes. Male and female subjects underwent three treatments: inhalation of CO, hot-water immersion (HWI), and a combination of CO inhalation and HWI. On the CO inhalation visits, the volume of CO administered was 1.0mL/kg body weight for men and 0.8mL/kg body weight for women, and subjects breathed that volume twice, each bout lasting 10 minutes. This volume of CO was intended to raise blood carbon monoxide saturation to 10-15% and reduce functional oxygen saturation to 85-90% to simulate a moderate altitude. On the heat visits, subjects sat in a hot tub heated to 40°C for 45 minutes. An intravenous (IV) catheter was placed for all study visits to collect venous blood at baseline and every hour after treatment for six hours. Whole blood was spun and the serum stored at -80°C until analysis. The serum was analyzed for EPO concentration at all time points using an ELISA kit. Baseline inflammation was analyzed using a multi-plex flow cytometry assay (Human Inflammation Panel 1, BioLegend) that measures the following inflammatory proteins: interleukins (IL)-1β, -6, -8, -10, -12p70, -17A, -18, -23, and -33; interferons (IFN)-α2, -γ; tumor necrosis factor (TNF)-α; and monocyte chemoattractant protein (MCP)-1. All interventions were found to increase concentrations of EPO. Contrary to our hypothesis, there were no additive effects of CO inhalation and hot water immersion. A positive linear relationship was found between peak EPO concentration and baseline IL-18 concentration, although the reasoning for this relationship must be explored further. | en_US |
| dc.identifier.uri | https://hdl.handle.net/1794/28896 | |
| dc.language.iso | en | en_US |
| dc.publisher | University of Oregon | en_US |
| dc.rights | Creative Commons BY-NC-ND 4.0-US | en_US |
| dc.subject | erythropoietin | en_US |
| dc.subject | inflammation | en_US |
| dc.subject | cytokines | en_US |
| dc.subject | heat | en_US |
| dc.subject | carbon monoxide | en_US |
| dc.subject | hypoxia | en_US |
| dc.title | Relationship between Baseline Inflammation and Peak Erythropoietin Levels in People Undergoing Carbon Monoxide Inhalation and Hot Water Immersion | en_US |
| dc.type | Thesis / Dissertation | en_US |