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Tuesday, 30 August 2016

A New Therapeutic Option in Place of Antibiotics in Fighting Life-threatening Bacteria.

Hepatic Cirrhosis is a progressive disease in which healthy liver tissue is replaced with scar tissue, eventually preventing the liver from functioning properly. The scar tissue blocks the flow of blood through the liver and slows the processing of nutrients, hormones, drugs, and naturally produced toxins. This is usually caused by prolong exposure to toxins such as alcohol and viral infection leading to death, several of which is reported yearly. Over a long period up to decades liver cirrhosis develops, and due to its proximity to the intestine leakage of intestinal bacteria enters the liver via the blood.  

                                                           Picture from Google Image
Prof. Dr. Jonel Trebicka from the Department of Internal Medicine in the University Hospital Bonn, attributed about one-third of cirrhosis cases to bacterial infection, a conclusion made from his experience in studying liver cirrhosis for many years. At the Institute for Experimental Immunology in the University Hospital Bonn, a team led by Dr. Zeinab Abdullah alongside those from the Institute of Molecular Immunology in the Technical University Munich, led by Prof. Dr. Percy Knolle aimed to find out the reason behind low immunity exhibited by patients with hepatic cirrhosis. have impaired immunity. This they discovered after intense research using animal model.
It was discovered that mice with liver cirrhosis produces Type-1 interferon in response to the intestinal bacteria by macrophages and monocytes in the liver. Further infection of these immune cells with lower loads of pathogenic bacteria (Listeria sp.), there was a massive production of Type-1 interferon. Therefore, the immune-regulatory factor interleukin-10 was release, which led to a defect in the anti-bacterial functions of the macrophages resulting to serious infection. When human monocytes from blood of patients suffering from cirrhosis were used in place of test mice; Dr. Zeinab Abdullah, a group leader at the Institute for Experimental Immunology in the University hospital Bonn said: "Following infection with pathogenic bacteria, we also observed highly elevated production of Type-1 interferon and interleukin-10 by monocytes from cirrhosis patients". "Our results identify the blind spot of the immune system that is responsible for the failure of the immune response to bacterial infections".
Further experiments identified new therapeutic options: This is where it gets interesting; even though gut bacteria is implicated in the liver there was no Listeria infection as observed in mice that cannot produce Type-1 interferon. Inability to produce Type-interferon inadvertently affects the production of interleukin-10 despite Listeria infection. "The groundbreaking finding of our study is that we might now be able to treat a life-threatening bacterial infection without antibiotics, simply by strengthening the immune response", says Prof. Dr. Percy Knolle of TU Munich. Hence, there is hope for new therapeutic options at least when it comes to treating Liver cirrhosis. "When the formation of Type-1 interferon in the liver cells is blocked by suitable substances, there is a prospect of reinvigorating the immune system", adds Professor Knolle. Conversely, as usual with drug discovery an extensive clinical studies and trial have to be carried out.

Article: Carl-Philipp Hackstein, Lisa Mareike Assmus, Meike Welz, Sabine Klein, Timo Schwandt, Joachim Schultze, Irmgard Förster, Fabian Gondorf, Marc Beyer, Daniela Kroy, Christian Kurts, Jonel Trebicka, Wolfgang Kastenmüller, Percy A Knolle, Zeinab Abdullah (2016) “Gut Microbial Translocation Corrupts Myeloid Cell Function to Control Bacterial Infection during Liver Cirrhosis”  Gut, doi:10.1136/gutjnl-2015-311224


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