New Therapeutic Approaches Using Hydrogen Sulfide Donors in Inflammation and Immune Response

Inflammation and immune response are associated with many pathological disorders, including rheumatoid arthritis, lupus, heart failure, and cancer(s). In recent times, important roles of hydrogen sulfide (H₂S) have been evidenced by researchers in inflammatory responses, as well as immunomodulatory effects in several disease models. Numerous biological targets, including cytochrome c oxidase, various kinases, enzymes involved in epigenetic changes, transcription factors, namely nuclear factor kappa B and nuclear factor erythroid 2-related factor 2, and several membrane ion channels, are shown to be sensitive to H₂S and have been widely investigated in various preclinical models. A complete understanding of the effects of H₂S in inflammatory and immune response is vital in the development of novel H₂S generating therapeutics. In this review, the biological effects and pharmacological properties of H₂S in inflammation and immune response are addressed. The review also covers some of the novel H₂S releasing prodrugs developed in recent years as tools to study this fascinating molecule. H₂S plays important roles in inflammation and immunity-related processes. Future researches are needed to further assess the immunomodulatory effects of H₂S and to assist in the design of more efficient H₂S carrier systems, or drug formulations, for the management of immune-related conditions in humans. Antioxid. Redox Signal. 35, 341-356.