More bad press for free radicals. Now it seems that too many of them can impair the mouse immune system, making them unable to fight off flu.
The finding could shed light on the cause of many mysterious human immunodeficiency disorders, such as severe combined immunodeficiency (SCID), says at the University of Iowa, Iowa city.
Free radicals are natural by-products of metabolism, which bind to molecules, including proteins and DNA. But oxidative damage is linked to many diseases such as lung cancer, atherosclerosis and Alzheimer鈥檚.
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However, no one knew if free radicals also affected an important arm of the immune system which uses T-cells. A type of white blood cell, T-cells are supposed to attack invaders but they can also malfunction, leading to autoimmune disorders.
Domann and colleagues created mice with elevated levels of a free radical called superoxide by knocking out the gene SOD2, which normally mops up superoxide.
Elevated levels of superoxide had 鈥渟evere effects on T-cell development,鈥� says Domann.
Normally, when T-cells are no longer working properly they self-destruct in a process called apoptosis. This is to prevent them attacking the body鈥檚 own cells.
According to Domann, excess free radicals appear to alter the signalling process responsible for apoptosis, prompting functional T-cells to suicide unnecessarily. 鈥淪uperoxide makes these cells die in very high numbers,鈥� he says.
Since a properly functioning SOD2 is fundamental to all mammals 鈥渨e would expect a similar result in humans鈥�, says Domann.
Without a complete repertoire of T-cells the mice were unable to fight off flu. All died when their immune system faced H1N1 compared to only 20 per cent of healthy mice.
The other side of the story
Domann reasoned that too few free radicals might also lead to problems. 鈥淚t鈥檚 the flip side,鈥� he says. 鈥淲ithout enough oxidants, dysfunctional T-cells aren鈥檛 encouraged to self-destruct.鈥�
To test the theory, Domann gave healthy mice antioxidant drugs. It boosted their T-cell count, but did not improve their recovery from influenza when compared with untreated mice. Domann hypothesises that the extra T-cells probably aren鈥檛 functional and should normally have died.
While in this short-term study the mice did not acquire autoimmune disorders, 鈥渇ree radicals have to remain on the table as a culprit鈥� and tested in future studies, he says.
a molecular biologist at Monash University, Australia says, 鈥淭he assumption is that free radicals are detrimental, but that鈥檚 not true.鈥� This study shows that both oxidants and antioxidants 鈥渉ave an important role鈥� in the immune system, he says.
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