NEOPTERIN AUGMENTATION OF TUMOR-NECROSIS-FACTOR PRODUCTION

Gamma interferon (gamma-IFN), lipopolysaccharide (LPS)-gamma or interleukin-2 (IL-2)-induced tumor necrosis factor-alpha (TNF-alpha) production by both macrophages and peripheral blood mononuclear cells (PBMC), was increased in the presence of neopterin. Addition of neopterin caused an increased level of TNF-alpha, but did not affect the kinetics of the TNF-alpha-production, which showed peak levels of cytotoxic activity 4 h after stimulatory treatment. Using anticytokine antibodies, we concluded that the neopterin effect was mainly gamma-IFN mediated, and only slightly affected by anti IL-2 receptor antibodies. The neopterin augmented TNF-alpha-production can be attributed to an immunological role for neopterin in the enhancement of cell-mediated immune (CMI) response.