Title: MyD88-dependant IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals.
Authors: Chun-Jen Chen, Yan Shi, Arron Hearn, Kate Fitzgerald, Doglas Goldenbock, George Reed, Shizuo Akira, and Kenneth L. Rock
Source: The Journal of Clinical Investigation Volume 116 Number 8 August 2006
PODIATRIC RELEVANCE:
Since the beginning of the study and practice of medicine, the disease of gout has plagued many. As early as the 27th century BCE, priest-physician Imhotep attempted the first recorded treatment of the disease. In the 18th century the causative agent in gout was proven to be uric acid crystals, also known as monosodium urate (MSU). These crystals trigger the devastatingly painful acute inflammatory attack known as gout.
METHODS:
After injection of MSU crystals into joints and peritoneal cavities of mice, a rapid and reproducible gouty attack was caused. This was characterized by acute inflammation and neutrophil infiltration within six hours. At six and 16 hours after injection, exudate cells were analyzed for neutrophil counts. The results were then compared with wild type and mutant mice to screen various proposed signaling and adapter molecules in the inflammatory pathway.
RESULTS:
No decrease in neutrophil infiltration was noted in the Toll/IL-1 Receptor (TLR) deficient versus wild type mice. This suggests TLR does not play a significant role in this pathway. TLR requires the MyD88 adapter molecule. Results suggested this adapter was crucial to this inflammatory response. The receptors of MyD88 adapter were well known to be Interleukin-1 (IL-1). IL-1 was similarly shown to be necessary to the inflammatory response. These results were verified by obtaining mutants deficient in MyD88 and IL-1. Both neutrophil counts were reduced by more than 85% after 6 and 16 hours.
COMMENTS:
With the patient population commonly seen in podiatric medicine, any new information on this disease will be welcomed by those charged with its treatment. Following the elucidation of the pathway for gouty inflammation, scientists and physicians become one step closer to treatment and prevention.
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Disclaimer:
Scientific Abstract Monthly postings are submitted by podiatric surgical residents. The ideas presented are not the opinions of the American College of Foot and Ankle Surgeons (ACFAS), nor are they presented as facts. ACFAS presents this information without any warranty of any kind, expressed or implied, and is not liable for its accuracy nor for any loss or damage caused by the user's reliance on information obtained in these areas.