We have to get very ill in order to get well more quickly

HZI researchers discover possible reason why the flu takes longer in elderly people


Influenza virus, magnified by electron microscopy

© HZI / Rohde

Elderly people get the flu more often and suffer from the symptoms for longer than younger people. Why this is the case was unclear - until now. Researchers at Helmholtz Centre for Infection Research (HZI) in Braunschweig, Germany, discovered a possible reason: Influenza virus proliferates slowly in elderly people that their immune system recognises the disease too late. The researchers published their results in the professional magazine, "Journal of Virology". 

With increasing age, people often suffer longer from the symptoms of the flu - and the same is true with mice. Until now professionals in the field presumed that this phenomenon was based on a weakened immune response allowing the infection to prosper. The Systems Immunology Department of the HZI headed by Prof Michael Meyer-Hermann proposed several mathematical models in collaboration with colleagues in the USA and their models suggest a different cause: A shift in the equilibrium of messenger substances of the immune system in elderly people changes the cells that are used as host cells by the virus.

One of the processes described by the mathematical model is the proliferation of the virus in epithelial cells of the lung. Exposed to the influence of certain messenger substances called cytokines, these host cells can change and become more resistant to the virus than the host cells of younger people. This slows the proliferation of the virus. The cytokines responsible for this effect are present at a higher basal concentration in elderly patients. Researchers call this phenomenon "inflammaging", as it is related to both "inflammation" and "aging". "We observed the largest difference in cytokine levels between the different age groups during the first 24 hours after infection," says Dr Esteban Hernandez-Vargas, one of the HZI scientists involved in this research. "The later differences are basically consequences of these early differences," adds Sebastian Binder from the System Immunology Department.

This causes the virus to proliferate more slowly in elderly people. As a result, the induction of the immune system is less pronounced and this slows down the defence reaction by the cells of the immune system. What sound paradox at first, makes sense if one looks more closely: Only if a certain stimulatory threshold is exceeded, the immune defence becomes active at full force and then fights the infection rapidly. In the absence of this process, the infection remains. "In order to get healthy again quickly, it is necessary to get really ill first," says Meyer-Hermann. 

Based on these insights, the researchers are now looking for ways to intervene in the infectious process that goes on during a flu. One approach would be a therapy that is based on, and possibly corrects, the changed cytokine equilibrium. Meyer-Hermann and colleagues intend to investigate next how this can be implemented.

Aside from the system immunologists from Braunschweig, staff members of the HZI departments of infection genetics and vaccinology as well as researchers of various US institutions, including Los Alamos National Laboratory in New Mexico, contributed to the recently published study. The System-Immunology Department is one of the HZI groups at Braunschweig Integrated Centre for Systems Biology, also called BRICS, which has been established by the HZI and Technical University Braunschweig. 

Original Publication:


Esteban A. Hernandez-Vargas, Esther Wilk, Laetitia Canini, Franklin R. Toapanta, Sebastian Binder, Alexey Uvarovskii, Ted M. Ross, Carlos A. Guzman, Alan S.Perelson, Michael Meyer-Hermann
The effects of aging on influenza virus infection dynamics
Journal of Virology, 2014, doi: 10.1128/JVI.03644-13