Vitamin D puts a brake on activated macrophages

How a newly discovered mechanism keeps inflammation under control

When macrophages, the first line defender cells of the immune system become activated, they produce an inhibitor, which acts back on them to suppress their activity. This has been revealed by the work of scientists at the German Research Centre for Biotechnology (GBF) in Braunschweig together with colleagues at the Hannover Medical School and at the University of Münster. The suppressor turned out to be an “old acquaintance”: vitamin D3, already well known, particularly for its role in bone metabolism. The scientists have now published their findings in the journal Blood.

Macrophages are the immune system’s “body guards”. They are patrolling the body’s blood and lymph system eating up everything that might be foreign or dangerous for the body – whether these are bacteria, breakdown products or foreign particles. The ingested material is then presented to other specialized immune cells, which determine whether or not these particles constitute a danger for the organism.

If a danger is sensed, interferon-? is released in response – a chemical alarm signal, which acts back on the macrophages and stimulates them. They now accumulate at the site of the danger signal and employ their whole arsenal of biochemical weaponry against the invader. This includes among others hydrogen peroxide, which the macrophages use to kill and neutralize ingested pathogens. The organ or tissue where the defender cells accumulate and go into action is referred to as being “inflamed” by the doctor.

According to the discoveries of the GBF researchers however, as macrophages join this battle they can release vitamin D3, which begins to rein them in after a while and reduces their aggressiveness. A possible explanation for this mechanism is that it functions as a “self-regulatory device of the immune system” suggests the former GBF Ph.D. student, Dr. Laura Helming, who discovered the mechanism while working on her Ph.D. thesis and who is working now as a postdoctoral fellow at Oxford University: “The purpose may be suppression of the inflammatory reaction, before it overshoots the mark”. If this would happen, it could prove to be more dangerous to the organism than the invader itself. Uncontrolled, activated macrophages can cause severe damage and even total destruction of body tissue. Thus, the incorporated vitamin D3 brake makes sure that the body’s own body guards are kept back soon after their activation.

Project leader, Dr. Andreas Lengeling, believes that this discovery may well have medical applications: “The better we understand this mechanism, the easier it will be to develop therapies for chronic inflammatory disorders”, he says.