Hope for new therapeutic approaches against hemorrhagic fever
With various viral infections such as Ebola infections, a hemorrhagic fever is part of the symptoms, which in addition to high fever also includes internal bleeding, liver and kidney damage. Often this virus infection leads to a fatal circulatory shock.
Scientists at the University of Basel have now successfully identified messenger substances from the immune system that lead to shock states in mice with hemorrhagic fever. By blocking the messenger substances, according to the researchers, new possibilities for the treatment of hemorrhagic fever are opened. The scientists have published their results in the specialist magazine "Cell Host & Microbe".
Fatal cardiovascular failure threatens
Hemorrhagic fever can be triggered by various viral infections. This also includes infections with the Lena virus from the arena virus family, which is transmitted from rodents in West Africa to humans and causes tens of thousands of deaths annually from hemorrhagic fever, the scientists explain. In the final stages, there are often shock conditions or fatal circulatory failure, although the underlying mechanisms have so far largely remained unclear.
Excessive inflammatory response the cause
In his current study, the research team led by Prof. Daniel Pinschewer from the Department of Biomedicine at the University of Basel investigated the causes of the shock states in hemorrhagic fever and found that an excessive inflammatory reaction, which is caused by the viruses, is an important cause of circulatory failure after arena virus infections.
Immune cells paradoxically contribute to the development of the disease
In previous work, Prof. Pinschewer's group had already demonstrated that the immune cells can paradoxically contribute to the development of the disease when infected with the Lassavirus. In the case of virus infections, the T cells take over a central component of our body's defenses, but the overzealous T cells apparently stimulate phagocytes to produce large amounts of nitrogen monoxide (NO) in the event of an arena virus infection. Although this is an important defense mechanism against bacterial infections, it does not help against viruses, the scientists explain.
If the messenger is blocked, there is no circulatory collapse
In the experiments on mice infected with arenavirus, it became clear that the nitrogen monoxide dilates the blood vessels and leads to the exudation of fluid into the tissue, which causes a decrease in the effective blood volume and ultimately a circulatory collapse. The scientists were also able to demonstrate that the NO production of the phagocytes requires the messenger substance interferon-gamma, as it is produced by T cells. If "this messenger substance was blocked with medication, the mice remained susceptible to the viral infection, but they did not suffer a circulatory collapse and survived largely unscathed," according to the University of Basel.
Hope for timely improvements in therapy
To date, the treatment options for Lassavirus infection and other viral hemorrhagic fevers remain inadequate, according to the researchers. However, the current study results offer hope. Because drugs to block interferon-gamma or its effects are already used in humans and the results of the present study could now contribute to the fact that these drugs will also be used successfully in the future for the treatment of hemorrhagic fever. (fp)