Arthritis Drug May Aid Bladder Inflammation
A drug commonly used to treat rheumatoid arthritis might also be effective against bladder inflammation, a condition that affects the health of millions — primarily women — by causing pain and impaired functioning, according to a recent Cedars-Sinai study published in the Journal of Biological Chemistry.
In the United States alone, up to 7.9 million women may have inflammation-associated bladder function impairment that is severe enough to impact their quality of life, the article stated. While events such as infections, radiation treatment and chemotherapy may trigger the condition, the cause often is unknown. Treatments for chronic bladder inflammation are limited to relieving symptoms.
Neil Bhowmick, PhD
The new study, led by Neil Bhowmick, PhD, director of the Cancer Biology Program at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, focused on a paradox of bladder inflammation: Cells in the bladder muscle of affected individuals both multiply and die at abnormally high rates. Using mouse models, Bhowmick and his colleagues identified a mechanism that underlies these two seemingly contradictory occurrences.
In further tests, the researchers found that the arthritis drug anakinra slowed down cell growth, or hyperplasia, and reduced inflammation without significantly accelerating cell death in the bladder muscles of mice. Anakinra is an antagonist for IL-1β, a protein involved in activating the white blood cells of the immune system. But in this case, the drug had a direct effect on bladder smooth muscle cells.
Although Bhowmick was looking to assess a potential side effect of a common chemotherapy agent in inducing bladder inflammation in his mouse models, the processes he studied are common to many types of bladder inflammation, he explained. These types include interstitial cystitis, a chronic condition whose origins are unknown. The researcher said he hopes his findings could one day help improve patients' lives.
"The next step is clearly to look at interstitial cystitis patients and explore a Phase II clinical study with an IL-1β antagonist, with the endpoint of improving the quality of life and pain components," Bhowmick said.
Bhowmick's collaborators on the study included Subhash Haldar, PhD, a postdoctoral fellow in his laboratory, and Christopher Dru, MD, a Urology resident, who together identified the mechanism behind concurrent cell death and growth in the bladder muscle; and Moshe Arditi, MD, executive vice chair of research in the Department of Pediatrics, director of the Division of Pediatric Infectious Diseases, Allergy and Immunology and professor of Pediatrics, who had identified relevant components of signaling pathways in the cells and provided transgenic models.
Citation: Haldar S, Dru C, Choudhury D, Mishra R, Fernandez A, Biondi S, Liu Z, Shimada K, Arditi M, Bhowmick NA. Inflammation and pyroptosis mediate muscle expansion in an interleukin-1β (il-1β)-dependent manner [published online ahead of print Jan. 16, 2015]. J Biol Chem. 2015; 290:6574-6583. doi: 10.1074/jbc.M114.617886.