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Background: Antarctica is a challenging environment for humans. It serves as a spaceflight ground analog, reflecting some conditions of long‐duration exploration class space missions. The French‐Italian Concordia station in interior Antarctica is a high‐fidelity analog, located 1000 km from the coast, at an altitude of 3232 m. The aim of this field study was to characterize the extent, dynamics, and key mechanisms of the immune adaptation in humans overwintering at Concordia for 1 year. Methods: This study assessed immune functions in fourteen crewmembers. Quantitative and phenotypic analyses from human blood were performed using onsite flow cytometry together with specific tests on receptor‐dependent and receptor‐independent functional innate and adaptive immune responses. Transcriptome analyses and quantitative identification of key response genes were assessed. Results: Dynamic immune activation and a two‐step escalation/activation pattern were observed. The early phase was characterized by moderately sensitized global immune responses, while after 3‐4 months, immune responses were highly upregulated. The cytokine responses to an ex vivo stimulation were markedly raised above baseline levels. These functional observations were reflected at the gene transcriptional level in particular through the modulation of hypoxia‐driven pathways. Conclusions: This study revealed unique insights into the extent, dynamics, and genetics of immune dysfunctions in humans exposed for 1 year to the Antarctic environment at the Concordia station. The scale of immune function was imbalanced toward a sensitizing of inflammatory pathways. Overview of changes during 1 year at Concordia station; Abbreviations: ADA = adenosine deaminase; ADORA2B = adenosine A2B receptor; HIF1A = hypoxia‐inducible factor 1‐alpha; VEGFA = vascular endothelial growth factor A; ICAM1 = intercellular adhesion molecule 1; SLAMF1 = signaling lymphocytic activation molecule 1; BTLA = B‐ and T‐lymphocyte attenuator [ABSTRACT FROM AUTHOR]

Altered TNF-[Alpha], glucose, insulin, and amino acids in islets of Langerhans cultured in a microgravity model system. Am J Physiol Endocrinol Metab 280: E92-E102, 2001.--The present studies were designed to determine effects of a microgravity model system upon lipopolysaccharide (LPS)-stimulated tumor necrosis factor-[Alpha] (TNF-[Alpha]) activity and indexes of insulin and fuel homeostasis of pancreatic islets of Langerhans. Islets (1,726 [+ or -] 117, 150 islet equivalent units) from Wistar-Furth rats were treated as 1) high aspect ratio vessel (HARV) cell culture, 2) HARV plus LPS, 3) static culture, and 4) static culture plus LPS. TNF-[Alpha] (L929 cytotoxicity assay) was significantly increased in LPS-induced HARV and static cultures; yet the increase was more pronounced in the static culture group (P [is less than] 0.05). A decrease in insulin concentration was demonstrated in the LPS-stimulated HARV culture (P [is less than] 0.05). We observed a greater glucose concentration and increased disappearance of arginine in islets cultured in HARVs. Although nitrogenous compound analysis indicated a ubiquitous reliance on glutamine in all experimental groups, arginine was converted to ornithine at a twofold greater rate in the islets cultured in the HARV microgravity model system (P [is less than] 0.05). These studies demonstrate alterations in LPS-induced TNF-[Alpha] production of pancreatic islets of Langerhans, favoring a lesser TNF activity in the HARV. These alterations in fuel homeostasis may be promulgated by gravity-averaged cell culture methods or by three-dimensional cell assembly. tumor necrosis factor-[Alpha]; cytokines; diabetes; amino acids

Background: Although a state of anemia is perceived to be associated with spaceflight, to date a peripheral blood hematologic assessment of red blood cell (RBC) indices has not been performed during long-duration space missions. Methods: This investigation collected whole blood samples from astronauts participating in up to 6-months orbital spaceflight, and returned those samples (ambient storage) to Earth for analysis. As samples were always collected near undock of a returning vehicle, the delay from collection to analysis never exceeded 48 h. As a subset of a larger immunologic investigation, a complete blood count was performed. A parallel stability study of the effect of a 48 h delay on these parameters assisted interpretation of the in-flight data. Results: We report that the RBC and hemoglobin were significantly elevated during flight, both parameters deemed stable through the delay of sample return. Although the stability data showed hematocrit to be mildly elevated at +48 h, there was an in-flight increase in hematocrit that was ~3-fold higher in magnitude than the anticipated increase due to the delay in processing. Conclusions: While susceptible to the possible influence of dehydration or plasma volume alterations, these results suggest astronauts do not develop persistent anemia during spaceflight. [ABSTRACT FROM AUTHOR]

Astronauts are exposed to increased body iron stores and radiation, both of which can cause oxidative damage leading to negative health effects. The purpose of this study was to investigate combined effects of high dietary iron (650 mg/kg diet) and radiation exposure (0.375 Gy cesium-137 every other day for 16 d) on markers of oxidative stress, immune system function, and colon mucosal environment in male Sprague-Dawley rats (n=8/group). Control rats consumed adequate iron (45 mg/kg diet) and were not irradiated. Combined treatments increased liver glutathione peroxidase, serum catalase, and colon myeloperoxidase while decreasing total fecal short-chain fatty acid concentrations. The high-iron diet alone increased leukocyte count. Radiation decreased the T-cell CD4: CD8 ratio. Plasma iron was negatively correlated with cytokine production in activated monocytes. Genes involved in colon microbial signaling, immune response, and injury repair were altered by radiation. Genes involved with injury repair and pathogen recognition changed with dietary iron. These data demonstrate that dietary iron and radiation, alone and combined, contribute to oxidative stress that is related to immune system alterations in circulation and the colon. The model presented may help us better understand the changes to these systems that have been identified among astronauts. [ABSTRACT FROM AUTHOR]