The hormone hepcidin may trigger the onset psoriasis, according to new research in Nature Communications.
In mammals, hepcidin is responsible for regulating iron levels in the body. Studies going back 50 years have reported high iron concentrations in the skin cells of psoriatic patients, however the cause of this excess and its significance to the condition have remained unclear until now. The new study is the first to name hepcidin as the likely link.
Researchers hpe that the finding will lead to the development of new drugs able to block the action of the hormone. Patients most likely to benefit from such a treatment are those with pustular psoriasis (PP).
“A new treatment targeting iron hormone imbalance in the skin offers hope,” says study author Charareh Pourzand from the Department of Life Sciences, the Centre for Therapeutic Innovation and the Centre for Bioengineering and Biomedical Technologies at the University of Bath in the UK, in a news release. “This innovative approach could significantly enhance the quality of life for millions, restoring their confidence and wellbeing.”
Hepcidin is responsible for controlling how much iron is absorbed from food and later released into the body. In healthy individuals, Hepcidin is produced exclusively in the liver, however the new study has found that in people with psoriasis, the hormone is also generated in the skin.
In the new study, mice developed a rodent form of psoriasis after being exposed to high levels of skin-produced hepcidin.
This over-abundance of the hormone caused the animals’ skin cells to retain far more iron than was required. In turn, this excess iron triggered both a hyperproliferation of skin cells and an abnormally high concentration of inflammation-inducing neutrophils in the topmost layer of skin.
These two outcomes are main features of human psoriasis.
She says: “Our data strongly suggests hepcidin would be a good target for skin psoriasis treatment. A drug that can control this hormone could be used to treat flare-ups and keep patients in remission to prevent recurrence.
“Also, by adjusting the excess iron in psoriatic skin with customised iron chelators (substances that bind to excess iron in the body and help remove it), we would aim to halt the uncontrolled proliferation of psoriatic skin cells. This hyperproliferation is a major focus of our laboratory’s research on psoriasis therapy, conducted in collaboration with national and international scientists from the Skin@Bath Network, including those from this study.”
Dr William Tillett, a senior lecturer at the University of Bath and a consultant rheumatologist specialising in the diagnosis and treatment of psoriatic arthritis, says: “This research from Dr Pourzand and colleagues is an exciting step forward for people living with psoriasis and for the clinical teams treating them.
“We don’t know exactly why people develop psoriasis but the identification of hepcidin as an important factor in the development of the disease opens doors not only to potential new treatments but also to the possibility of preventing the disease developing in people at high risk. Existing drugs – called biologics – can be highly effective but they are costly and rationed in the UK. Furthermore, these drugs don’t work for everyone and they can stop working after a while, so a new approach to treatment would be very welcome.”
He adds: “However, developing drugs is notoriously time consuming and costly, so a new treatment won’t be available immediately and it’s important for patients to manage expectations.”
Dr Penelope Pratsou, a consultant dermatologist and spokesperson for the UK charity the British Skin Foundation, says: “The findings of this study shed new light on the pathophysiology of psoriasis, with hepcidin overabundance in psoriatic skin thought to be another culprit. These results appear promising for patients, though more research is required to further elucidate the role of hepcidin and its potential as a prospective treatment target in psoriasis.”
