Hydrogen sulfide and inflammation: the good, the bad, the ugly and the promising

Hydrogen sulfide is rapidly gaining ground as a physiological mediator of inflammation, but there is no clear consensus as to its precise role in inflammatory signaling. This article discusses the disparate anti-inflammatory ('the good') and proinflammatory ('the bad') effects of endogenous and pharmacological H(2)S in disparate animal model and cell culture systems. We also discuss 'the ugly', such as problems of using wholly specific inhibitors of enzymatic H(2)S synthesis, and the use of pharmacological donor compounds, which release H(2)S too quickly to be physiologically representative of endogenous H(2)S synthesis. Furthermore, recently developed slow-release H(2)S donors, which offer a more physiological approach to understanding the complex role of H(2)S in acute and chronic inflammation ('the promising') are discussed.