Hibernation as anti-inflammatory agent

Animals that hibernate have a reduced supply of oxygen and markedly lower body temperature, yet they can survive the winter without damage to their organs. They achieve this by almost completely shutting down their immune systems. Researchers at the University of Groningen discovered that the drop in body temperature is what causes white blood cells to be stored in the lymph glands. A strongly bioactive lipid, known as sphingosine-1-phosphate (S1P), regulates the temporary storage of white blood cells, but it also ensures that these cells return to the bloodstream after hibernation. A team of researchers from the University Medical Center Groningen (UMCG)/University of Groningen, including H. Bouma, F. Kroese and R. Henning, published the results of their research in the leading scientific journal PNAS. They think that this hibernation principle can also be used to suppress the immune responses of patients and so prevent organ damage, for example to intensive care patients or during major operations. 

During the cold winter months, when there is little food to be had, many animals go into hibernation to conserve energy. During hibernation, major transformations take place in various bodily functions, without any damage occurring to the organs. Bouma, Kroese and Henning’s research revealed that the immune system of hamsters shuts down almost completely during hibernation, because more than 95% of their white blood cells leave the bloodstream. The researchers showed for the first time that these white blood cells are temporarily stored in lymph glands, and return to the bloodstream as soon as the animal leaves hibernation. This temporary storage proves to be regulated entirely by low body temperature, which naturally occurs when hamsters hibernate. The researchers also demonstrated that white blood cells also leave the bloodstream when the body temperature of non-hibernating animals, such as rats, is lowered. They demonstrated that the storage and reintroduction of white blood cells is regulated by changing the blood levels of a lipid, known as sphingosine-1-phosphate (S1P), in the blood. This lipid turns out to be produced and released by red blood cells, and its action is dependent on temperature. During the temporary storage of white blood cells, the immune system is put on ‘standby’, but is ready for a quick restart after hibernation. The storage ensures that the immune system’s ‘memory’ is saved and may also lead to more efficient energy conservation. On the downside, this suppression of the immune system is probably playing a major role in the rapid spread of White Nose Syndrome, a recent outbreak of fungal infection in hibernating bats that is threatening entire species with extinction in the United States.
 
Bouma believes that this newly discovered hibernation mechanism could be applied to suppress patients’ immune responses. It perhaps could be used to further improve the technique of cooling patients, presently used to limit organ damage after heart operations. The occurrence of organ damage after these operations is a much-feared complication, whereby inflammation induced by the immune system probably plays a major role. New medicines could be developed to suppress patients’ immune responses on the basis of the newly discovered mechanism.
 
Hjalmar Bouma began studying medicine in 2004 and is combining his studies with PhD research on the immunological aspects of hibernation and their potential clinical applications. Frans Kroese is Professor of Cell Biology and Rob Henning is Professor of Pharmacology at the UMCG/University of Groningen. The results described here are the outcome of a collaboration between the departments of Clinical Pharmacology, Cell Biology and Anaesthesiology of the University Medical Center Groningen, the departments of Chronobiology and Mass Spectrometry of the University of Groningen and the University of Aberdeen’s Rowett Institute. 

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