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Anticancer drug can spur immune system to fight infection

Date:
April 1, 2015
Source:
Emory Health Sciences
Summary:
Imatinib, an example of a 'targeted therapy' against cancer, or related drugs might be tools to fight a variety of infections, scientists say. Imatinib, is an example of a "targeted therapy" against certain types of cancer. It blocks tyrosine kinase enzymes, which are dysregulated in cancers such as chronic myelogenous leukemia and gastrointestinal stromal tumors.
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At low doses, the anticancer drug imatinib can stimulate the bone marrow to produce more neutrophils (shown here), which are imporant for fighting bacterial infections.
Credit: Image courtesy of CDC

Low doses of the anti-cancer drug imatinib can spur the bone marrow to produce more innate immune cells to fight against bacterial infections, Emory researchers have found.

The results were published March 30, 2015 in the journal PLOS Pathogens.

The findings suggest imatinib, known commercially as Gleevec , or related drugs could help doctors treat a wide variety of infections, including those that are resistant to antibiotics, or in patients who have weakened immune systems. The research was performed in mice and on human bone marrow cells in vitro, but provides information on how to dose imatinib for new clinical applications.

"We think that low doses of imatinib are mimicking 'emergency hematopoiesis,' a normal early response to infection," says senior author Daniel Kalman, PhD, professor of pathology and laboratory medicine at Emory University School of Medicine.

Imatinib, is an example of a "targeted therapy" against certain types of cancer. It blocks tyrosine kinase enzymes, which are dysregulated in cancers such as chronic myelogenous leukemia and gastrointestinal stromal tumors.

Imatinib also inhibits normal forms of these enzymes that are found in healthy cells. Several pathogens -- both bacteria and viruses -- exploit these enzymes as they transit into, through, or out of human cells. Researchers have previously found that imatinib or related drugs can inhibit infection of cells by pathogens that are very different from each other, including tuberculosis bacteria and Ebola virus.

In the new PLOS Pathogens paper, Emory investigators show that imatinib can push the immune system to combat a variety of bacteria, even those that do not exploit Abl enzymes. The drug does so by stimulating the bone marrow to make more neutrophils and macrophages, immune cells that are important for resisting bacterial infection.

"This was surprising because there are reports that imatinib can be immunosuppressive in some patients," Kalman says. "Our data suggest that at sub-clinical doses, imatinib can stimulate bone marrow stem cells to produce several types of myeloid cells, such as neutrophils and macrophages, and trigger their exodus from the bone marrow. However, higher doses appear to inhibit this process."

The authors note that imatinib appears to stimulate several types of white blood cells, which may provide a limit on inflammation, rather than increasing neutrophils only, which can be harmful. The authors go on to suggest that imatinib or related drugs may be useful in treating a variety of infections in patients whose immune system is compromised, such as those receiving chemotherapy for cancer.


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Materials provided by Emory Health Sciences. Note: Content may be edited for style and length.


Journal Reference:

  1. Ruth J. Napier, Brian A. Norris, Alyson Swimm, Cynthia R. Giver, Wayne A. C. Harris, Julie Laval, Brooke A. Napier, Gopi Patel, Ryan Crump, Zhenghong Peng, William Bornmann, Bali Pulendran, R. Mark Buller, David S. Weiss, Rabindra Tirouvanziam, Edmund K. Waller, Daniel Kalman. Low Doses of Imatinib Induce Myelopoiesis and Enhance Host Anti-microbial Immunity. PLOS Pathogens, 2015; 11 (3): e1004770 DOI: 10.1371/journal.ppat.1004770

Cite This Page:

Emory Health Sciences. "Anticancer drug can spur immune system to fight infection." ScienceDaily. ScienceDaily, 1 April 2015. <www.sciencedaily.com/releases/2015/04/150401115744.htm>.
Emory Health Sciences. (2015, April 1). Anticancer drug can spur immune system to fight infection. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2015/04/150401115744.htm
Emory Health Sciences. "Anticancer drug can spur immune system to fight infection." ScienceDaily. www.sciencedaily.com/releases/2015/04/150401115744.htm (accessed May 23, 2017).

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