Neopterin-induced suppression of erythropoietin production in vitro

The production of neopterin increases in several diseases with activation of the cellular immune response. As previously shown serum concentrations of neopterin are inversely correlated with blood hemoglobin concentrations in the anemia of hematological and malignant disorders. Besides the role of chronic immune activation on the disturbed iron metabolism, an inhibitory influence of pteridines on cellular erythropoietin production could not be excluded. To test the possibility that pteridines are able to suppress the hypoxia-induced production of erythropoietin, the effects of neopterin and 7,8-dihydroneopterin on the human cell line HepG2 (hepatocellular carcinoma) were investigated. 24 h incubation with neopterin induced a dose-dependent reduction of erythropoietin production. The erythropoietin concentration significantly decreased by '57.6% with 300 pM and by '34.9% with 100 μM neopterin, respectively. 7,8 dihydroneopterin did not influence erythropoietin production. The inhibitory effect of neopterin on erythropoietin production was a consequence of reduced erythropoietin-mRNA levels. The results of this study show a neopterin-induced suppression of hypoxia-induced erythropoietin formation in HepG2 cultures in a dose dependent manner. We speculate that under in vivo conditions high concentrations of neopterin can aggravate the anemia of chronic disease.