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Fungal infections cause life-threatening sepsis
Fungal infections can lead to life-threatening inflammatory reactions in the human organism. Often it is not the causative agent itself, but the "excessive inflammatory immune response" that causes the "fatal consequences", the researchers led by Karl Kuchler from MedUni Vienna write in the journal "PLoS Pathogens".
According to a statement by the Medical University of Vienna, the scientists have "deciphered the molecular causes of life-threatening inflammatory reactions that are caused by fungal infections." Fungal infections are often the cause of blood poisoning (sepsis), particularly in immunocompromised people. "In intensive care units, sepsis is the second leading cause of death worldwide, and life-threatening Candida fungal infections pose a high risk of sepsis, especially in severely immunodeficient patients," said Kuchler and colleagues.
Excessive inflammatory immune response in fungal infections The group led by Karl Kuchler in the CD laboratory at MedUni Vienna (Christian Doppler Laboratory for Infection Biology, Max F. Perutz Laboratories at the Campus Vienna Biocenter) found out how the excessive inflammatory immune response in fungal infections, which is mostly for the life-threatening consequences - for example organ damage - is responsible, takes place at the molecular level and how it can possibly be blocked. According to the results of Kuchler and colleagues, "two highly aggressive types of phagocytes of the immune system (neutrophils and inflammatory monocytes), which, however, also have a high potential for collateral destruction", play an essential role in the inflammatory response of the Candida infection. Special interferons, which are released as messengers of the immune system in fungal infections, stimulate the immigration of these immune cell types into infected organs and thus cause sepsis, the researchers report
Blocking the inflammatory response prevents sepsis The scientists were able to prove not only how the fungal infections lead to life-threatening blood poisoning, but also found that the "pharmacological reduction in monocytes and neutrophils through treatment with pioglitazone" has a positive effect here. "We were able to show for the first time that the targeted blocking of this immune response with anti-inflammatory drugs significantly reduces Candida sepsis and thus mortality," explained Karl Kuchler. The anti-inflammatory drug pioglitazone has long been known and is used, among other things, to treat type II diabetes. In the experiment with mice "the drug and the drug specifically reduced the number and activity of neutrophils and inflammatory monocytes and increased the survival rate in the case of invasive Candida infections," according to the Medical University of Vienna.
Discovery opens up new therapeutic approaches According to the research team led by Karl Kuchler, "the targeted blocking of excessive immune reactions could result in new therapeutic approaches to increase the chances of a cure for a life-threatening fungal sepsis." This would open up additional scope for infection prevention and treatment. The far-reaching significance of the discovery becomes clear when you consider that infectious diseases are the number one cause of death worldwide and the pathogenic fungi are responsible for particularly dangerous infections. According to the MedUni Vienna announcement, “More than 6 billion euros are spent each year on antifungal medications, and the total costs for the medical treatment of infectious diseases caused by pathogenic fungi exceed triple-digit billions.” Here, the new treatment approach could not only be a significant improvement for the benefit of the patient represent, but also relieve the health system from a financial point of view. It is irrelevant whether the previously tested active ingredient pioglitazone is used or better alternatives are found. What is crucial is the discovery of the molecular mechanism of action and the general option to block the inflammatory reactions. (fp)
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