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Researchers discover human immune system has emergency backup plan
Date:12/20/2010

nvasive bacterial infection, and that the IL-1β system provides an important safety net when NF-κB falls short.

"Having a backup system in place is critical given the diverse strategies that bacterial pathogens have evolved to avoid bacterial clearance," said Victor Nizet, MD, professor of pediatrics and pharmacy, whose laboratory conducted the infectious challenge experiments in the study. "A number of bacteria are known to suppress pathways required for NF-κB activation, so IL-1β signaling could help us recognize and respond to these threats."

While helpful in short-term defense against a severe bacterial infection, the dramatic increase in neutrophil counts seen in the NF-κB-deficient mice ultimately came at a cost. Over many weeks, these activated immune cells produced inflammation in multiple organs and led to the premature death of the animals. Long-term blockade of NF-κB signaling has been explored extensively by the biotechnology and pharmaceutical industry as a strategy for anti-inflammatory or anti-cancer therapy, perhaps unaware of the risks suggested by this new research.

"One might contemplate adding a second inhibitor of IL-1β signaling to protect against the over-exuberant neutrophil response," said Karin. "Unfortunately, loss of both the NF-κB pathway and the backup IL-1β pathway rendered the mice highly susceptible to invasive bacterial infection which they no longer cleared."

Altogether, the UC San Diego research sheds new light on the complex and elegant regulatory pathways required for a highly effective innate immune system. The scientists noted that future investigations must take into account these interrelationships in order to design novel drugs against inflammatory diseases that achieve their treatment goals while minimizing the risk of infection.


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Contact: Scott LaFee
slafee@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

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