An Inflammatory Question

prostate cancer
Elizabeth Platz and Nrupen Bhavsar: Interleukin-10 
may help protect against prostate cancer by blocking 

For several years now, a multidisciplinary team of investigators at Johns Hopkins has been trying to figure out whether inflammation (and the body's immune response) has anything to do with prostate cancer. Several findings suggest that it does; for example, pathologists Angelo De Marzo and Jonathan Epstein have identified and characterized a type of inflammation found in biopsied prostate cells that seems to be a precursor to PIN (prostatic intraepithelial neoplasia), a type of "funny-looking" cells often found near cancer cells. Geneticist William Isaacs is studying genes related to the body's ability to fight inflammation that may be disabled in cancer. Oncologist William Nelson has spent years looking at the oxidative damage to cells caused by certain foods, and investigating possible steps between this oxidative damage, inflammation and cancer.

And epidemiologist Elizabeth Platz, Sc.D., M.P.H., The Martin D. Abeloff, M.D. Scholar in Cancer Prevention has led several important studies focusing on inflammation, including looking at the role of non-steroidal antiinflammatory drugs (NSA IDs) as possible preventive agents in prostate cancer, and studying the potential of statin drugs, which lower cholesterol and are anti-inflammatory, to also lower the risk of developing prostate cancer. Recently, Platz and colleagues have conducted studies probing possible links between immune system-related factors and prostate cancer.

Men who have higher levels of a naturally 
occurring chemical called interleukin-10 
have a lower risk of developing prostate cancer, 
and of having it come back after treatment.

Part of their research has focused on a naturally occurring chemical called interleukin- 10 (IL-10). This is a cytokine, an anti-inflammatory agent that regulates the body's ability to fight off countless foreign invaders including germs, pollen, and even cancer. Her team recently reported that men who produce more IL-10 were associated with lower risks of prostate cancer developing and recurring after treatment. Platz speculates that IL-10 may help protect against prostate cancer by blocking production of inflammatory agents. It also may put up roadblocks that hinder cancer's ability to spread beyond the prostate. With support from the Patrick C. Walsh Prostate Cancer Research Fund, the investigators' next step was to look for a link between the risk of prostate cancer and blood levels of IL-10 or other cytokines, measured months to years before the diagnosis. The A. Ross Myers family donated the money that supported this project. 

"We studied 268 men with prostate cancer and 268 men without the diagnosis," says Platz. "All of these men were participants in the CLUE II cohort study of Washington County, Maryland. They enrolled in the study back in 1989 and provided a blood specimen, and they've been followed ever since." Platz and colleagues found that while blood levels of IL-10 were about the same in men with prostate cancer and in men without, men of normal weight who had more IL-10 had a lower risk of prostate cancer. Interestingly, there seemed to be no such link in men who were overweight or obese. However, in all men, heavy or thin, the risk of prostate cancer was also lower when higher levels of some other cytokines were present.

Maybe one day, if scientists can boost
the levels of the body's most promising 
antiinflammatory agents, 
they can help keep cancer from starting, 
or help stop it from spreading.

Based on the evidence from this study, Platz and colleagues hope to learn more about how IL-10 and other cytokines help protect the body from cancer. It may be that one day, if they zero in on the most promising antiinflammatory agents, scientists will be able to boost these levels in men with and without cancer, and that this may help keep cancer from starting, or help stop it from spreading. 

This work was also conducted by Nrupen Bhavsar, a post-doctoral fellow, Alan Meeker, Sarah Peskoe, Charles Drake, Angelo De Marzo, William Isaacs, and Jay Bream, a Johns Hopkins Bloomberg School of Public Health expert in the biology of IL-10.

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