Sci. Aging Knowl. Environ., 10 September 2003
Vol. 2003, Issue 36, p. nw124
[DOI: 10.1126/sageke.2003.36.nw124]


Starve a Neuron, Feed Pneumonia

Mice reveal immune changes that might render stroke patients susceptible to infection

R. John Davenport;2003/36/nw124

Key Words: {beta}-adrenoreceptor • lymphocytes • ischemia • propranolol

Strokes not only paralyze muscles, they numb the immune system too, and a new study reveals why. The research on mice suggests that strokes leave their victims vulnerable to infection because they reduce amounts of a key antibacterial molecule. The result offers the first explanation for elevated infection rates after stroke, a phenomenon that doctors have known about for decades.

When a stroke halts the blood supply to part of the brain, neurons often die, causing paralysis, speech impairments, or sometimes death. But even if people survive the initial trauma, they aren't in the clear. Many patients die from infections such as pneumonia. Scientists suspected that the body suppresses the immune system to prevent an inflammation overload that might exacerbate brain damage, but no one had identified the changes that promote infection.

To investigate that question, Prass and colleagues gave mice strokes by surgically blocking a blood vessel in the brain. Three days later, all animals had raging bacterial infections in their lungs and blood, but control mice subjected to a sham operation remained infection-free. The team analyzed immune cells from the sick rodents' blood and spleen and found reduced numbers of T and NK cells, both of which are crucial for combating noxious bacteria.

Further experiments revealed that the remaining immune cells malfunction. The researchers grew blood cells in culture, then treated them with molecules that normally activate antibacterial defenses. Compared with their counterparts from sham-operated animals, cells from infected mice churned out less interferon {gamma} (IFN-{gamma}), a molecule that activates cells that gobble up bacteria, and more interleukin-4, which shuts down such cells.

Next the team injected ill animals with immune cells from healthy rodents. Numbers of infected bacteria dropped dramatically. However, an infusion of cells from animals that can't produce IFN-{gamma} did not ward off bacteria, further suggesting that a dearth of the molecule promotes infection after stroke.

Brain injury from stroke or other trauma induces stress responses by activating the sympathetic nervous system, which governs bodily functions such as heartbeat and breathing. To investigate whether this system promotes infection, the researchers injected poststroke animals with compounds that block sympathetic nerve signals. The treatment increased production of IFN-{gamma}, reduced bacterial infection, and improved survival. The results suggest that strokes prod the sympathetic nervous system to shut down immunity, which likely opens the door for bacterial invasion.

Previously, researchers focused on inflammation immediately following a stroke, but what happens to the immune system later has received little attention, says stroke researcher Florence Hofman of the University of Southern California in Los Angeles. The new study explores that stage. "They nicely show that IFN-{gamma} is critical," she says. Surgery is a stress, she notes, but the sham-operated animals responded differently, indicating that "there's something about [stroke] that's different from other kinds of trauma." If scientists verify the result in humans, they might uncover new treatments to minimize brain damage while staving off infection.

--R. John Davenport; suggested by Amir Sadighi Akha

September 10, 2003
  1. K. Prass et al., Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation. J. Exp. Med. 198, 725-736 (2003). [Abstract/Free Full Text]
Citation: R. J. Davenport, Starve a Neuron, Feed Pneumonia. Sci. SAGE KE 2003 (36), nw124 (2003).

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