JCI online early table of contents: April 1, 2008

EDITOR'S PICK: Unraveling how a drug helps patients with multiple sclerosis

Although the drug IFN-beta is commonly used to treat individuals with the relapsing-remitting form of multiple sclerosis (MS), little is known about the mechanism(s) by which it acts. However, Genhong Cheng and colleagues, at the University of California at Los Angeles, have now reported a mechanistic pathway by which it reduces disease in a mouse model of MS known as EAE.

In addition to being a drug, IFN-beta is produced naturally by the body during certain immune responses. In the study, mice lacking a component of the molecule to which IFN-beta binds to mediate its effects were found to develop more severe EAE than mice expressing this protein. This was associated with increased numbers of immune cells known as Th17 cells in the central nervous system of the mice, the part of the body affected in individuals with MS. Further experiments showed that disease could be alleviated in these mice by administration of a soluble molecule known as IL-27, leading the authors to suggest that in individuals with MS, the beneficial effects of IFN-beta are likely to be mediated, at least in part, through its ability to induce the secretion of IL-27.

TITLE: The type I IFN induction pathway constrains Th17-mediated autoimmune inflammation in mice

AUTHOR CONTACT:
Genhong Cheng
University of California at Los Angeles, Los Angeles, California, USA.
Phone: (310) 825-8896; Fax: (310) 206-5553. Email: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=33342

EDITOR'S PICK: New approach to limiting organ damage in individuals with sickle cell disease

Sickle cell disease (SCD) is so called because of the abnormal sickle shape of the red blood cells in individuals with this blood disorder. The abnormal shape of the red blood cells prevents them passing easily through blood vessels, which can become obstructed such that blood flow to an organ is restricted, causing pain and organ damage. An episode of blood vessel obstruction is known as a vaso-occlusive crisis (VOC) and a new study, performed by Pierre-Louis Tharaux and colleagues, at INSERM U689, France, has indicated that a drug known as bosentan prevents experimentally induced VOC in a mouse model of SCD.

In vivo analysis indicated that during experimentally induced VOC, blood vessel resistance was increased through a process mediated by the protein endothelin. As bosentan, which is used to treat individuals with pulmonary arterial hypertension, is a drug that acts as an antagonist of both endothelin receptors, the authors assessed its ability to treat experimentally induced VOC in a mouse model of SCD. The drug was found to have many beneficial effects that cumulated to prevent the death of the mice, leading to the suggestion that bosentan might provide a new way to limit VOC, and thereby organ damage, in individuals with SCD.