Cytokine induction of neopterin production

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Abstract
The pteridine neopterin is a marker of immunological activation and has been shown to be a useful marker of graft-versus-host disease (GVHD) in bone marrow transplant patients. High levels of both neopterin and interferon-gamma (IFN-γ) were produced in vitro during mixed lymphocyte responses, which may be considered to be a model of the primary events leading to GVHD. Neopterin was shown to be produced by monocytes in response to stimulation with IFN-γ, but not other cytokines. However, the interleukins IL-lα, IL-1β, IL-2, and tumour necrosis factor (TNF) alpha and beta, but not IL-6, stimulated neopterin production by unfractionated peripheral blood mononuclear cells (PBMC), and culture supernatants from PBMC stimulated with IL-1 α, 1L-1 β, IL-2 and IL-6, but not TNF-α or TNF-β induced neopterin production following transfer to fresh monocyte cultures. It therefore appears that cytokines may generate neopterin by induction of IFN-γ, by synergy with low levels of induced IFN-γ, or by non-IFN-γ-dependent mechanisms.