Chronic inflammatory inflammatory disease is difficult to treat and entails a risk of complications, including the development of intestine cancer. Young people are particularly affected: when genetic predisposition and certain factors coincide, diseases such as ulcerative colitis or Crohn’s disease generally manifest between the ages of 15 and 29, a critical period for education and the development of the early career. Rapid diagnosis and treatment are crucial. Investigators at Charité – Universitätsmedizin Berlin have now discovered a therapeutic objective that contributes significantly to stop the ongoing inflammatory processes. Its findings are published in the current number of the magazine Nature immunology.
Sometimes gradually, sometimes in shoots, accompanied by severe abdominal cramps, diarrhea, weight loss, fatigue and a high level of emotional stress, this is like the two most common chronic inflammatory diseases, Crohn’s disease and ulcerative colitis, often begin. Although ulcerative colitis only affects the internal coating of the large intestine, Crohn’s disease can involve all the thickness of the intestinal wall, more commonly in the thin intestine, but sometimes also the stomach and esophagus. Continuous inflammation can cause lasting tissue damage and increase the risk of cancer. Although traditional treatments aim to suppress the immune system as a whole, the newest therapies are more specific: they interrupt the inflammatory process by blocking specific messengers that drive inflammation in the body.
The exact causes of severe systemic diseases are not yet fully understood until today. In addition to genetic factors, it is also believed that environmental influences play an important role in their development. Professor Ahmed Hegazy has been studying inflammatory processes in the intestine and the defense mechanisms of the immune system in the Department of Gastroenterology, Infectiatology and Rheumatology of Charité for several years. Together with his team, he has now managed to identify the interaction between two messenger substances of the immune system such as the driving force behind chronic intestinal inflammation: Interleucin-22, a protein that supports the cells that cover the interior of the intestine and helps maintain the protective barrier and the Oncostatina M, a signaling molecule that plays a role of tissue repair and a significant reflection.
Un controlled chain reaction
“In the clinic, we see mainly young patients who just begin their professional life. Until now, we have only been able to stop the progression of the disease and relieve symptoms. But not all patients respond well to existing treatments, so new therapeutic approaches are urgently needed,” says Ahmed Hegazy. In previous works, the research team closely examined the effects of Oncostatina M, a messenger molecule that promotes inflammation. This protein, produced by certain immune cells, activates other inflammatory factors: triggering a chain reaction that triggers an excessive immune response. “It was especially interesting for us to see that patients with high levels of Oncostatina M do not respond to several common therapies,” explains Ahmed Hegazy. “This means that Oncostatina M levels could help predict treatment failure and can serve as a biomarker for a more serious disease. There is exactly where we focused our efforts: we wanted to better understand this signaling route and find ways to block it with specific treatments.”
The research team spent five years discovering how the Messenger Immune Oncostatina M triggers inflammatory responses. They began through the use of animal models, and then studied patient tissue samples, to examine the different stages of chronic intestinal diseases, the sequencing of individual avant -garde cells showed that, compared to health to produce inflammatory inflammatory protein. Interestingly, interleucin-22, which normally protects the tissue, also makes the intestinal lining more sensitive to oncostatin M by increasing the number of its receptors. “These two immune messengers work together and amplify inflammation, attracting more intestine immune cells, such as a fire that continues to obtain more fuel and propagation,” says Ahmed Hegazy. “In our models, we specifically block the union sites for Oncostatina M and saw a clear reduction in both chronic inflammation and cancer associate.”
Therapy directed for high -risk patients at sight
The researchers found a particularly high number of receptors for the Messenger Molecule of Oncostatina M around tumors in tissue samples of patients with colorectal cancer caused by chronic intestinal inflammation, but not in the surrounding healthy tissue. This observation suggests that this signaling route can help promote cancer development. However, chronic inflammation does not always lead to intestine cancer, and not all patients are affected in the same way. “Chronic inflammatory diseases of the intestine are highly complex and differ from person to person. That is exactly what makes them so difficult to treat and predict treatment,” says Professor Britta Siegmund, director of the Gastroenterology, Infectiatology and Reumatology Clinic. “Thanks to the role of Oncostatina M and its amplifier interaction with interleucin-22, which we have now identified, we have a clearer understanding of what is promoting chronic inflammation in some patients. This opens the door to the development and proof of a new therapeutic approach.”
The experimental findings of the team can soon translate into a real world therapy: by specifically interrupting the harmful interaction between interleucin-22 immune messengers and Oncostatina M. “Our results provide a strong scientific basis to develop specific treatments against this mechanism for the promotion of inflammation in inflammatory disease, particularly in patients with more serious ways of the disease of inflammation. Clinic to test an antibody that blocks receptors for oncostatin M.