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Hypoxia frequently associated with certain physiologic and pathologic conditions influences numerous cellular functions. Because the effects of short-term hypoxia are incompletely understood, we examined phagocytosis and cytokine production as well as the activation of the transcription factors HIF-1 and NFκB in peripheral blood cells of healthy volunteers exposed to an oxygen concentration equivalent to that found at a height of 5500 m. Furthermore, we analysed plasma HIF-1 and serum concentrations of various HIF-1-dependent genes. Results showed that short-term hypoxia increased phagocytosis in neutrophils without affecting monocyte phagocytosis. Hypoxia decreased basal TNFα concentration in monocytes and basal interferon γ concentration in CD4+ T lymphocytes. In contrast, plasma HIF and serum VEGF concentrations were not affected by hypoxia, although serum EPO concentration was raised. In PBMC, hypoxia increased cytosolic HIF-1 concentration without affecting nuclear HIF-1 concentration and led to a rise in the nuclear NFκB in PBMC. Our results show that short-term hypoxia affects immune functions in healthy individuals. Furthermore, we speculate that the effects of hypoxia are not due to HIF-1, but are caused by the activation of NFκB .

Objectives. Obesity and related diseases are dramatically increasing problems, particularly in children and adolescents. We determined circulating levels of different interleukin (IL)-1 family members in normal weight and overweight adolescents. Methods. Seventy male, Caucasian adolescents (13–17 years) were recruited. Thirty-five had a body-mass index (BMI) above the 90th age-specific percentile. IL-1α, IL-1β, IL-1 receptor antagonist (IL-1ra), and IL-18 were determined using multiplex-technology. Results. IL-18 concentrations were higher in the overweight group compared to normal weight (161.6±40.7 pg/ml versus 134.7±43.4 pg/ml, P=.009). Concentrations of circulating IL-1β levels were below the detection threshold. IL-18 (R2:0.355, P

Chronic heart failure (CHF) is associated with elevated concentrations of tumor necrosis factor (TNF) and cardiotrophin-1 (CT-1) and altered peripheral blood mononuclear cell (PBMC) function. Therefore, we tested whether CT-1 induces TNF in PBMC of healthy volunteers. CT-1 induced in PBMC TNF protein in the supernatant and TNF mRNA in a concentration- and time-dependent manner determined by ELISA and real-time PCR, respectively. Maximal TNF protein was achieved with 100 ng/mL CT-1 after 3–6 hours and maximal TNF mRNA induction after 1 hour. ELISA data were confirmed using immunofluorescent flow cytometry. Inhibitor studies with actinomycin D and brefeldin A showed that both protein synthesis and intracellular transport are essential for CT-1 induced TNF expression. CT-1 caused a dose dependent nuclear factor (NF) B translocation. Parthenolide inhibited both NFB translocation and TNF protein expression indicating that NFB seems to be necessary. We revealed a new mechanism for elevated serum TNF concentrations and PBMC activation in CHF besides the hypothesis of PBMC activation by bacterial translocation from the gut.