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