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HIF-1 Study may benefit patients with AIDS and Flesh Eating Virus

July 6th 2005

Graphic depicting HIF-1 control of white blood cells’ bacterial killing efficiency
Credit: Victor Nizet, UCSD

Increasing the level of a protein known as hypoxia inducible transcription factor-1 ( HIF-1) in the body.  According to the research team white blood cells respond directly to Streptococcus, Staphylococcus, Salmonella, and other bacteria that cause disease in humans, by increasing their levels. The HIF-1 protein, in turn, stimulates white blood cells to release antimicrobial compounds that kill bacteria.

In a collaborative effort between the laboratories of Randall Johnson, UCSD professor of biology and Victor Nizet, associate professor of pediatrics at the UCSD School of Medicine, research has found that treating white blood cells with chemicals to increase HIF-1 levels could enhance the cells’ capacity to kill bacteria.

In this study, the researchers compared how well macrophages in which HIF-1 levels were elevated, normal or zero could kill bacteria, including Streptococcus isolated from a patient with flesh-eating disease. They found that the greater the HIF-1 levels in white blood cells, the greater their bacterial killing power. They also found that mice lacking HIF-1 in their macrophages and neutrophils were less able to combat skin infections than normal mice.


“The placement of essential microbial killing functions of white blood cells under regulation of HIF-1 represents an elegant controlled response system,” explained Johnson. “The white blood cells are in a resting state as they circulate in the oxygen-rich bloodstream, but can then be activated in response to the declining oxygen gradient encountered upon migration to sites of infection. Direct encounter with the bacteria then activates the neutrophils and macrophages maximally. Under HIF-1 regulation, antimicrobial genes are expressed only in infected tissues and not in healthy tissues where they could produce unwanted inflammatory damage.”

The research will hopefully benefit patients with weakened immune systems.  “These findings suggest a potential novel approach to treatment of difficult infections such as those produced by antibiotic resistant bacteria or those affecting patients with weakened immune systems due to chronic disease, cancer chemotherapy or AIDS,” said Nizet. “Rather than designing drugs to target the bacteria, medications that promote HIF-1 activity could be used to boost the bacterial killing ability of white blood cells and promote the resolution of infection through the actions of our natural immune defenses.”

The study will be published in the July, 2005 issue of The Journal of Clinical Investigation.

By Dan Wilson
Best Syndication Staff Writer



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Copyright 2005 Best Syndication                                            Last Updated Sunday, July 11, 2010 01:18 AM