Hypoxia-inducible factors (HIFs) are the key transcription factors for the cellular adaptation to hypoxia. They consist of a constitutively expressed b-subunit and an oxygen-sensitive a-subunit (HIF-1a, -2a). It is well-known that HIF-1a is also regulated by lipopolysaccharides (LPS) and inflammatory cytokines. HIFs are critically involved in cell metabolism and differentiation indicating an integrative role for HIFs in adaptation of monocytes during extravasation into inflamed tissue. Therefore we wanted to examine the time course of HIF expression and the expression of the HIF-regulating prolyl hydroxylases (PHDs) in the human monocytic cell line THP-1 for up to 72 hours. Furthermore we focussed on potential HIF-mediated effects on glucose consumption induced by hypoxia and inflammatory mediators. THP-1 cells were kept under normoxic (21% O₂) and hypoxic (3% O₂) conditions with or without LPS (1 mg/ml) stimulation for up to 72 hours. Proteins were detected in whole cell lysates by immuno blot; mRNA expression was analyzed by real-time PCR. Long-term stimulation with LPS caused a persistent increase of HIF-1a mRNA under normoxic and hypoxic conditions. In contrast, hypoxia or LPS stimulation alone reduced HIF-2a mRNA levels whereas the combination of LPS and hypoxia showed no additive effect on HIF-2a mRNA expression. LPS-induced HIF-1a protein accumulation was only detectable for up to 48 hours under normoxia, whereas HIF-2a protein accumulation persisted. Moreover LPS declined the glucose consumption of THP-1 cells under hypoxia. From our data we conclude that both, HIF-1a and HIF-2a are regulated in monocytic cells and may contribute to the adaptation of these cells during extravasation.