Gamma Interferon Is Dispensable for Neopterin Production In Vivo

Abstract

Previous studies have indicated that neopterin is synthesized in vitro by human monocyte-derived macrophages and dendritic cells upon stimulation with gamma interferon (IFN-␥). Neopterin production under specific conditions in vitro has also been obtained upon stimulation with IFN-␣ and/or IFN-␤. However, it is unknown if any IFN-␥-independent neopterin synthesis is possible in vivo. In the present study we investigated the serum neopterin concentrations in patients affected by the syndrome of Mendelian susceptibility to mycobacterial disease (MSMD). Indeed, this syndrome is characterized by deeply impaired or absent IFN-␥ production or function due to severe mutations in molecules involved in IFN-␥/interleukin-12 (IL-12)/IL-23-dependent pathway. Serum neopterin levels were measured by an enzyme-linked immunosorbent assay in 27 patients with MSMD. We found that serum neopterin levels are elevated in the complete absence of IFN-␥ activity due either to a complete deficiency of its receptor or to deleterious mutations of IL-12 or its receptor. These data clearly indicate that, as reported from in vitro studies, other stimuli are able to induce neopterin synthesis in vivo. Consequently, neopterin cannot be used as means of diagnosis of MSMD due to IFN-␥-, IL-12-, and IL-23-dependent pathway defects.

Utility of CSF Cytokine/Chemokines as Markers of Active Intrathecal Inflammation: Comparison of Demyelinating, Anti-NMDAR and Enteroviral Encephalitis

“…However the reason for the observed discrepancies in CSF CXCL12 levels between ADEM and the other two groups of encephalitis (EVE and anti-NMDAR E) is not clear [ 50 ]. We did not see any correlation between CSF neopterin and IFN-γ or α (data not shown) in contrast to the previous hypothesis that IFN-γ and IFN-α induced neopterin synthesis [ 51 , 52 ] suggesting the possibility of alternate immune mechanisms of neopterin production [ 53 ].…”

Effect of perioperative autologous versus allogeneic blood transfusion on the immune system in gastric cancer patients

“…Interestingly, in this study despite a significant decrease in serum neopterin and IFN-γ cytokine in patients undergoing allogeneic blood transfusion, no correlation was observed between the two phenomena. This investigation was supported by Sghiri et al (2005), who demonstrated that IFN-γ is not the only stimulus in vivo needed for the synthesis of neopterin in patients with impairment of the IFN-γ pathway. Therefore, rather than the depressed secretion of IFN-γ cytokine, we speculate that allogeneic blood transfusion directly and/or by other cytokines down-regulates monocytes/macrophage function to exert their inhibitory and regulatory properties on neopterin production.…”

Response and Recovery in the Plasma Metabolome Tracks the Acute LCMV-Induced Immune Response

“…Plasma and urine neopterin levels increase in HIV/AIDS 38, cytomegalovirus infection, hepatitis A and B virus 39, and in other conditions which mediate the Th1 response 38. Neopterin is induced by IFN α/β and was recently shown to be produced in vivo independently of IFN-γ 40, indicating that other factors may be able to stimulate neopterin. Biopterin is biotransformed from neopterin, and similarly increased during the IFN-γ stimulated immune response.…”