ACE inhibitors and AT1R blockers suppress inflammation in mice

Aug 19 2009

Neuroinflammation and paralysis reversed in an animal model; Heidelberg neurologist publishes in the Proceedings of the National Academy of Sciences

Conventional blood pressure medication can treat inflammation in an animal model mimicking multiple sclerosis (MS). This discovery was made by Dr. Michael Platten, head consultant at the department of Neurooncology at Heidelberg University Hospital and head of the Helmholtz Experimental Neuroimmunology Junior Research Group on at the German Cancer Research Center and his team in cooperation with scientists from Stanford University in California. Blood pressure medication called ACE inhibitors and AT1R blockers can suppress inflammation in mice suffering from an autoimmune disease comparable to MS. The results are published in the Proceedings of the National Academy of Sciences (PNAS) back-to-back with a report of a Bochum team that also supports the new role for ACE inhibitors.

The renin-angiotensin-aldosterone system (RAAS) is a system of messengers and receptors that regulates blood pressure. The angiotensin-converting enzyme (ACE) produces angiotensin II, which increases blood pressure. This effect is mediated mainly via the angiotensin 1 receptor (AT1R). Medications that inhibit the ACE enzyme or block the AT1R receptor are used by millions to lower blood pressure. Scientific trials and clinical observations have increased the suspicion that RAAS also plays a decisive role in immunological processes.

In their tests, the Heidelberg researchers first showed that the RAAS was actually elevated in MS foci in the brains of deceased MS patients. They then treated mice that had an autoimmune disease of the nervous system similar to MS with ACE inhibitors and AT1R blockers. The results were astonishing - the drugs suppressed specific immune cells that were instrumental in promoting inflammation. In addition, they increased anti-inflammatory immune cells that reversed existing neuroinflammation and subsequent paralysis.

Since the animal model the researches employed is an established model that is frequently used for drug development in MS, the researchers hope that the results are transferable to humans. Clinical trials analyzing the efficacy of ACE inhibitors in MS patients are currently being planned. "The use of this blood pressure medication is an attractive strategy for treating autoimmune diseases. The drugs are already used by millions of people, are cheap, and have few side effects," explains Professor Lawrence Steinman, partner of the Heidelberg researchers at Stanford University.

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