Hydrogen therapy may be an effective and specific novel treatment for Acute Graft‐versus‐host disease (GVHD)

Liren Qian,Jianliang Shen

doi:10.1111/jcmm.12081

Liren Qian, Jianliang Shen

Open Access

https://doi.org/10.1111/jcmm.12081

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Abstract

Allogeneic haematopoietic stem cell transplantation (HSCT) has been widely used for the treatment of haematological malignant and non-malignant haematologic diseases. However, acute graft-versus-host disease (aGVHD) is a kind of severe complication of HSCT limiting its application. Cytokines such as tumour necrosis factor-α (TNF-α), IL-6 play an extremely important role in the formation and development of aGVHD. Besides, the oxidation phenomena and/or the formation of free radicals have been suggested to be causally related to various haematological disorders including aGVHD. Reactive oxygen species (ROS), such as hydroxyl radicals, play an important role in the formation and development of aGVHD. Hydrogen has been reported to have the ability to inhibit levels of cytokines such as TNF, IL-6 in vivo. Our recent studies provided evidence that hydrogen inhalation can selectively reduce cytotoxic oxygen radicals and exert antioxidant effects. Therefore, we suggested that hydrogen may have therapeutic effects on aGVHD. This hypothesis entails many experimentally testable predictions. We propose the experimental study by detecting complete blood counts (CBC) and Clinic signs of aGVHD mice. We also propose to detect the levels of TNF-α, IL-2, IL-1β, IL-6 which play important roles in the pathogenesis of aGVHD. To discover potential mechanisms of the therapeutic effects of hydrogen on the aGVHD model, we will examine gene-expression profiles. This study will open a new therapeutic avenue combining the field of therapeutic medical gases and aGVHD. This theory is original and probably of importance, because therapeutic medical gases have never been used for aGVHD previously.

Highlights

In 2007, Ohsawa et al [4]discovered that hydrogen gas has antioxidant and antiapoptotic properties that protect the brain against ischaemia–reperfusion injury and stroke by selectively neutralizing hydroxyl and peroxynitrite radicals
Vol 17, No 8, 2013 non-toxicity at any pressure [29]. It can penetrate biomembranes and diffuse into the cytosol, mitochondria and nucleus to protect nuclear DNA and mitochondria [30]. As those cytokines including IL-6, IL-1, tumour necrosis factor-a (TNF-a), et al and free radicals have been suggested to play great important roles in the formation and development of acute graft-versus-host disease (aGVHD) as discussed above, we suggested that hydrogen gas may be potentially effective for aGVHD by downregulating cytokines and selectively reducing hydroxyl and peroxynitrite radicals
On the basis of these experimental designs, we preliminarily demonstrated the therapeutic effects of hydrogen on aGVHD in a mice model [37]

Summary

Introduction

Hydrogen is the most abundant chemical element. Hydrogen gas has been extensively used in chemical field such as fuel processing, fertilizer production (3H2 + N2 ? 2NH3) and so on. In 2007, Ohsawa et al [4]discovered that hydrogen gas has antioxidant and antiapoptotic properties that protect the brain against ischaemia–reperfusion injury and stroke by selectively neutralizing hydroxyl and peroxynitrite radicals. Recent basic and clinical research has revealed that hydrogen is an important physiological regulatory factor with antioxidant, anti-inflammatory and antiapoptotic protective effects on cells and organs [5,6,7,8,9,10], proving that hydrogen could down-regulate cytokines, including CCL2, IL1b, IL-6, IL-12, TNF-a, etc.

Results

Conclusion