The potential role of neopterin in Covid-19: a new perspective

Abstract

Neopterin (NPT) is a member of pteridines group, synthesized by macrophages when stimulated by interferon gamma (INF-γ). NPT is regarded as a macrophage stimulation indicator, marker of cellular immune activation and T helper 1 (Th1) type 1 immune response. Here, we aimed to provide a view point on the NPT features and role in Covid-19. Serum NPT level is regarded as an independent prognostic factor for Covid-19 severity, with levels starting to increase from the 3rd day of SARS-CoV-2 infection, being associated with severe dyspnea, longer hospitalization period and complications. Also, early raise of NPT reflects monocytes/macrophages activation before antibody immune response, despite the NPT level may also remain high in Covid-19 patients or at the end of incubation period before the onset of clinical symptoms. On the other hand, NPT attenuates the activity of macrophage foam cells and is linked to endothelial inflammation through inhibition of adhesion molecules and monocytes migration. However, NPT also exerts anti-inflammatory and antioxidant effects by suppressing NF-κB signaling and NLRP3 inflammasomes. NPT can be viewed as a protective compensatory mechanism to counterpoise hyper-inflammation, oxidative stress, and associated organ damage.

Keywords: Covid-19 severity; Neopterin; SARS-CoV-2 infection.

Fig. 1

Activation of neopterin release and inhibition of adhesion molecules: T cells through tumor necrosis alpha (TNF-α), natural killer (NK) cells through interferon gamma (INF-γ) and viral infections through pathogen-associated molecular patterns (PAMPs) activate macrophage (M1) for release of neopterin (NPT), which inhibit release of adhesion molecules, monocyte chemoattractant protein-1 (MCP-1), intracellular adhesion molecule-1(ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1)

Fig. 2

The potential role of neopterin in SARS-CoV-2 infection: Neopterin (NPT) inhibits tissue injury, hyperinflammation and oxidative stress that are induced by SARS-CoV-2-mediated immune activation