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Jayanti et al. Neuroimmunol Neuroinflammation 2020;7:92-108 Neuroimmunology
DOI: 10.20517/2347-8659.2019.14 and Neuroinflammation

Review Open Access

Bilirubin and inflammation in neurodegenerative and
other neurological diseases

Sri Jayanti , Rita Moretti , Claudio Tiribelli , Silvia Gazzin 1
1
2
1
1 Italian Liver Foundation, Centro Studi Fegato, Trieste 34149, Italy.
2 Neurology Clinic, Department of Medical, Surgical, and Health Sciences, University of Trieste, Trieste 34139, Italy.
Correspondence to: Dr. Silvia Gazzin, Italian Liver Foundation, Bldg. Q, AREA Science Park, SS14; Km 163,5, Trieste 34149, Italy.
E-mail: silvia.gazzin@fegato.it

How to cite this article: Jayanti S, Moretti R, Tiribelli C, Gazzin S. Bilirubin and inflammation in neurodegenerative and other
neurological diseases. Neuroimmunol Neuroinflammation 2020;7:92-108. http://dx.doi.org/10.20517/2347-8659.2019.14

Received: 12 Nov 2019 First Decision: 2 Mar 2020 Revised: 14 Mar 2020 Accepted: 24 Mar 2020 Available online: 11 May 2020

Science Editor: Athanassios P. Kyritsis Copy Editor: Jing-Wen Zhang Production Editor: Jing Yu

Abstract

Inflammation links neurodegenerative, neuropsychiatric and other neurological diseases (NDs) with acute brain
events. It is responsible for the alteration of neurotransmission and circuity, brain architecture, and cell fate,
affecting mood and personality (anxiety, depression and schizophrenia) and behavior (decline in cognitive, motor
and speech abilities, altered sleep, fatigue, pain sensitivity and dementia). Inflammation is also a key component in
systemic chronic diseases (cardiovascular disease, cancer, diabetes, and metabolic syndrome), in which bilirubin
has been demonstrated to improve the diseases by acting as a multi-target antiinflammatory molecule, and where
the evaluation of pharmacological modulation of the pigment level as a therapeutic approach has already started.
While altered serum bilirubin levels have been reported in ND patients, the potential activity of bilirubin in the
brain is vague. This review summarizes the available fragmentary information on the interplay of bilirubin with
neuroinflammation, aiming to elucidate the pigment’s role in the central nervous system environment.

Keywords: Neuroinflammatory diseases, bilirubin, brain, heme oxygenase, biliverdin reductase, inflammation,
homeostasis

INTRODUCTION
Bilirubin (unconjugated - UCB) is the final metabolite of hemoglobin, which is processed in the
liver (by conjugation to 1 or 2 molecules of glucuronic acid - CB: conjugated bilirubin) before

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
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sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
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