Impact of Plasma 5 Hydroxyindoleacetic Acid, a Serotonin Metabolite, on Clinical Severity in Acute Respiratory Distress Syndrome

Takeshi Tanaka,Koichi Izumikawa,Masato Tashiro,Masahiko Mori

doi:10.3389/fmed.2021.785409

Abstract

Acute respiratory distress syndrome (ARDS) is characterized by dysregulated vascular permeability. The clinical outcomes remain poor, and the disease burden is widespread. We demonstrated that plasma 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, is a pivotal severity indicator of ARDS. Serotonin is an effector of cellular contraction and a modulator of vascular permeability. Plasma 5-HIAA levels were significantly elevated in severe ARDS cases with shock status (p = 0.047) and positively correlated with SOFA (p < 0.0001) and APACHE-II score (p < 0.0001). In the longitudinal analysis, plasma 5-HIAA levels were also a strong independent predictor of mortality rate (p = 0.005). This study indicates that plasma 5-HIAA is a biomarker of ARDS severity and highlights the importance of evaluating vascular leakage levels for ARDS treatment.

Highlights

The concept of acute respiratory distress syndrome (ARDS) was first introduced over 50 years ago [1]; its mechanism of pathogenesis remains poorly understood, while its disease burden is substantial
We recently reported the effect of plasma 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, on the clinical outcomes of sepsis [6], with an increase in plasma 5-HIAA levels in patients with severe septic shock
The plasma 5-HIAA levels were higher in the ARDS/shock+ group compared to the ARDS/shock- group (11.5 ng/mL vs. 7.1 ng/mL, p = 0.047) (Figure 1)

Summary

Introduction

The concept of acute respiratory distress syndrome (ARDS) was first introduced over 50 years ago [1]; its mechanism of pathogenesis remains poorly understood, while its disease burden is substantial. ARDS and septic shock are characterized by dysregulated vascular permeability [2]. One of the major mechanisms that regulate vascular permeability is cellular contraction [3], which can be induced via the serotonin and RhoA/Rho-associated protein kinase (ROCK) signaling pathway in certain cell types [4]. We recently reported the effect of plasma 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, on the clinical outcomes of sepsis [6], with an increase in plasma 5-HIAA levels in patients with severe septic shock. Burdens of vascular leak remain a large issue in several diseases, such as ARDS (any etiology including COVID-19), viral hemorrhagic fever, and dengue fever. Our conceptual hypothesis of the serotonin-ROCK pathway approach to regulating vascular permeability could be a common approach for all types of these

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