Pathogenic fungi common cause of blood poisoning

Fungal infections cause life-threatening sepsis

07/30/2012

Fungal infections can lead to life-threatening inflammatory reactions in the human organism. It is often not the pathogen itself, but the „excessive inflammatory immune response“ Cause of the „fatal consequences“, write the researchers around Karl Kuchler of the MedUni Vienna in the journal „PLoS pathogens“.

The scientists, according to the announcement of the Medical University of Vienna, „the molecular causes of life-threatening inflammatory reactions, which are caused by fungal infections, decrypted.“ The fungal infections are often the cause of blood poisoning, especially in immunocompromised persons (sepsis). „In intensive care units, sepsis is the second most common cause of death worldwide, and particularly in immunocompromised patients, life-threatening Candida fungal infections pose a high risk of sepsis“, so Kuchler and colleagues.

Excessive inflammatory immune response in fungal infections
The working group around Karl Kuchler in the CD-Laboratory of the MedUni Vienna (Christian Doppler Laboratory for Infection Biology, Max F. Perutz Laboratories at Campus Vienna Biocenter) has found out how the excess inflammatory immune response of the fungal infections, mostly for the life-threatening consequences - for example Organ damage - is responsible, at the molecular level, and how it can possibly be blocked. According to the results of Kuchler and colleagues play „Two highly aggressive types of phagocytes of the immune system (neutrophils and inflammatory monocytes), which also have high collateral destruction potential“, in the inflammatory reaction of Candida infection an essential role. Special interferons, which are released as messenger substances 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 of monocytes and neutrophils by treatment with pioglitazone“ Here a positive effect unfolds. „We were able to show for the first time that the targeted blockade of this immune response with anti-inflammatory drugs significantly reduces candida sepsis and thus mortality“, explained Karl Kuchler. The anti-inflammatory drug pioglitazone has been known for some time and is used, among other things, for the treatment of type II diabetes. I could try with mice „the administration of the drug specifically reduces the number and activity of neutrophils and inflammatory monocytes and increases the survival rate of invasive Candida infections“, so the message of the Medical University of Vienna.

Discovery opens new therapeutic approaches
According to the research team around Karl Kuchler could „Targeted blockade of excessive immune responses will provide new therapeutic approaches to increase the chances of recovery in 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 one considers that infectious diseases are the number one cause of death worldwide and the pathogenic fungi are responsible for particularly dangerous infections. According to information from MedUni Vienna „Every year more than 6 billion euros are spent on antifungal medicines, and the total cost of medical treatment of infectious diseases by pathogenic fungi exceeds hundreds of billions.“ Here, the new treatment approach could not only represent a significant improvement in terms of patients, but also relieve the health system from a financial point of view. Whether at the end of the already tested active ingredient pioglitazone is used or better alternatives are found, it is irrelevant. Crucial is the discovery of the molecular mechanism of action and the general option for blocking inflammatory reactions. (Fp)

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Picture credits: Gerd Altmann