Dear Colleagues,

Inflammation is involved in the pathophysiology of many diseases. Controlling the progression of inflammation has become a key goal in the treatment of these diseases. There are many therapies to treat inflammation, but their results are inconsistent. Therefore, it is necessary to search for new mechanisms of action of anti-inflammatory drugs and new drugs which will act on specific molecular targets.

Reactive oxygen species (ROS), play an important role in the development of many inflammatory diseases, and act as both a signaling molecule and a mediator of inflammation. ROS, such as superoxide, can rapidly combine with NO at a diffusion-limited rate to form reactive nitrogen species (RNS), such as peroxynitrite. RNS, in turn, induces nitrosative stress, which adds to the pro-inflammatory burden of ROS.

Thiols are compounds that possess a sulfhydryl (−SH) functional group. Thiol-containing drugs are used as chelators of heavy metal ions, removing them from the body and preventing them from blocking enzyme activity and promoting oxidation. Thiols and their conjugate bases, thiolates, are also good nucleophiles and are therefore reactive toward electrophilic species, including ROS/RNS. Thus, thiol drugs are used as ROS/RNS scavengers to prevent them from oxidizing proteins, lipids, and DNA. Glutathione (GSH) is an intracellular thiol antioxidant. It is the most abundant non-protein thiol, and is crucial for maintaining a favorable redox status in cells. Lower levels of GSH causes higher ROS production, which results in an imbalanced immune response, inflammation, and susceptibility to infection.

The sulfhydryl group is found in a number of drug compounds and confers several useful properties. Thiol-containing drugs can reduce radicals and other toxic electrophiles, restore cellular thiol pools, and form stable complexes with heavy metals. Thus, thiols can treat a variety of conditions by serving as radical scavengers, GSH prodrugs, or metal chelators. The many-faceted biochemistry of thiol compounds is the basis for their complex and varied roles in human health and disease. In recent years, the impetus to to use existing approved medications has renewed interest in thiol-containing drugs. However, the full realization of their potential as useful treatments for inflammatory diseases depends on continued investigation of these roles.

In this special issue, we would like to publish research on the effect of thiol compounds (drugs containing –SH group(s)) on inflammatory diseases at various levels from detailed molecular research to general in vivo models of inflammation. Those studies showing combinations of inflammation, oxidative/nitrosative stress and the action of thiol compounds are especially welcome. Topics could focus on but are not limited to:

- Physiological roles of endogenous thiol compounds in inflammation

- Pathological roles of both endogenous and exogenous thiol compounds in inflammation

- Therapeutic roles of thiol group donors in inflammation

- Side effects caused by sulfur drugs (including increasing inflammation)

Dr. Magdalena Kotańska
Guest Editor