US researchers found that a drug made from the root of the hydrangea plant, which has for centuries been used in Chinese medicine, showed promising results in treating autoimmune disorders such as rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, type 1 diabetes, eczema and psoriasis.

The study was the work of researchers from the Program in Cellular and Molecular Medicine and the Immune Disease Institute at Children’s Hospital Boston (PCMM/IDI), together with the Harvard School of Dental Medicine and was published in the 5 June 2009 issue of the journal Science.

An exciting new area in the field of autoimmune disease research is learning about the role of a particular immune system cell called the T helper 17 (Th17) which is genetically different from other types of CD4+ T cell like the Th1, Th2 and T-regulatory cells and appears to play a unique role in the part of the immune system that causes harm when it over-reacts.

The immune system is a complex of delicately balanced “seek and destroy” systems that recognize when something is wrong in the body and then trigger a response to repair the damage or eliminate foreign agents. However, when this delicate balance is disturbed, the responses switch on when there is nothing wrong, causing the immune system essentially to “attack” healthy tissue.

This is what happens in rheumatoid arthritis, where the overactive inflammatory response eventually destroys cartilage in the joints and even healthy tissue in places like the lungs or under the skin. Exactly how and why this happens is still a mystery, but the more scientist look into it, the more they discover that immune cells like the Th17 are involved in unique ways.

In this study, the authors report how a small molecule called halofuginone (extracted from hydrangea root) selectively stops Th17 cells being made, without affecting the other CD4+ T cells, thus showing how it might be possible to stop the immune system from over-producing harmful Th17 cell responses.

They also showed that halofuginone reduced disease symptoms in mice bred with autoimmune disorders.

In the body, cytokines cause Th17 cells to differentiate from other CD4+ T cells, but when the researchers collected cultured mouse CD4+ T cells along with the cytokines, they found that adding halofuginone made levels of Th17 go down significantly but not Th1, Th2 or T regulatory cells.

They also found a similar effect in cultured human CD4+ T-cells: halofuginone selectively stopped production of IL-17, the principal cytokine made by Th17 cells.

The reason this discovery is important is because there are currently no good treatments for autoimmune disorders because you can’t get in there and turn down just the inflammatory process without also turning down the protective processes that for instance protect patients from infections.

The main treatments currently rely on antibodies that neutralize cytokines, the chemical messengers that T cells use to control immune fuction and inflammatory responses.

But antibodies are expensive, have to be injected and/or infused, and don’t actually solve the root cause of the problem, they just mop up cytokines rather than stop them being produced in the first place. So patients have to keep coming back for infusions to keep the inflammation under control.

As a last resort you can give patients drugs that completely suppress the immune system but for obvious reasons this is very risky.

In this study the researchers appear to have found a way, using halofuginone as the fine tuning tool, to selectively reduce production of Th17 cells and thereby only switching off the inflammatory response without altering the function of other parts of the immune system. The other good thing about this discovery is that halofuginone can be taken by mouth: no injection necessary.

First author Dr Mark Sundrud, of the PCMM/IDI, said:

“This is really the first description of a small molecule that interferes with autoimmune pathology but is not a general immune suppressant.”

Written by: Catharine Paddock, PhD