Uric acid is principal mediator of immune response after tissue damage

Uric acid appears to be one of the major endogenous mediators of the immune response to injured and dying cells, biochemists report in the September 7th issue of Nature.

Not only could this discovery lead to more effective vaccines, both for infectious disease and as cancer immunotherapy, “it may be that uric acid is the missing link in how some autoimmune diseases get triggered and why allogenic transplants are rejected,” senior author Dr. Kenneth L. Rock told Reuters Health.Dr. Rock and colleagues at the University of Massachusetts Medical School in Worcester identified a low molecular weight fraction of cytosol from damaged mammalian cells that enhanced the cytotoxic T lymphocyte (CTL) response to HIV gp120 antigen. Further analysis revealed that the main constituent of this fraction is uric acid.When they treated cells with UV irradiation or heat shock to induce apoptosis, intracellular uric acid levels increased. Dr. Rock’s group suggests that degradation of nucleic acids liberates purines that in turn are converted into uric acid. Co-injection of uric acid and antigen stimulated dendritic cells, and accelerated dendritic cell expression of CD86 and CD80. The amount of uric acid needed to provide an adjuvant effect in mice was on par with the production of uric acid released from cells that die in tumors or during viral infections, they note.Dr. Rock hopes to test uric acid as an alternative to alum, the only adjuvant approved for human use, which is relatively weak. “Our most obvious concern” is that its use would be excessive inflammation at an injection site, he added. “But preliminary animal studies suggest that this is not the case.”Because of the recognition of uric acid as the causative agent of gout “we always viewed it as pathological,” Dr. Rock concluded. Instead, “this molecule may have that property because it communicates that there’s been tissue injury and danger, and what happens in gout patients is that they have an exaggeration of what is a normal reaction.”(Source: Nature 2003: www.nature.com/nature: Reuters Health: Karla Gale: September 10, 2003: Oncolink)