URIC ACID: A DEMONIZED ANGEL
Majid Ali, M.D.
Uric acid has been demonized by people who sell uric acid drugs. It is a powerful antioxidant, nearly fifty-fold stronger than vitamin C. Like all bodily antioxidants that act as anti-inflammatory substances, uric acid is an anti-inflammatory agent within the physiologic range. Other crucial physiologic roles of uric acid involve healing immune responses and autoimmune responses. Notably, the acid provides a molecular link between cell injury and immunity. Most fascinating, uric acid facilitates cellular cross-talk between dead and living cells. When the body is insulted and inflamed, it uses uric acid as one of its messengers. Just taking a drug to lower uric acid level is simply killing the messenger.
Uric acid is entrenched in the medical thinking, as well as in the minds of the general public, as a demon (usual laboratory blood level range : 3.6 to 8.5 mg/dL (~214 µmol/L). It is considered as the:
☞ Cause of gouty arthritis,
☞ Cause of uric acid stones,
☞ Risk factor for hypertension, and
☞ Risk factor for cardiovascular disorders.
The disturbing aspect of this sad story is that people who speak ill of uric acid do not think about its place in evolution’s intelligent design of the human body nor do they study its molecular biology to understand the true significance of changes in its blood levels.
Gout, A Disease of Celebrities
It seems to me that the public infatuation with the ‘disease-of-the-celebrities’ is not a new malady. The mystique of gout has been inculcated and perpetuated throughout history by many celebrities. Alexander the Great, Charlemagne, Benjamin Franklin, Leonardo da Vinci, Newton, and Darwin were among the luminaries who suffered from gout. Their accounts seemed to have fired the imagination of the public about swollen big toes.
Mammals generally have lower serum uric acid levels (0.5 to 1.0 mg/dL) than humans, owing to the existence in them of the enzyme uricase that converts uric acid into allantoin. Our homonoid ancestors lost that enzyme during the Miocene Epoch. Interestingly, it appears that resulted from several parallel mutations which initially involved the promoter region but eventually silenced the whole gene.
Uric Acid Facilitates Dead-Cell-Living-Cell Cross-talk
That uric acid is a principal endogenous danger signal released from dead and dying cells calls for a major shift in the way we look at this molecule. Uric acid stimulates dendritic cells to their maturation. When such cells are co-injected with antigen in vivo, CD8+ T cell responses are significantly enhanced by the generation of responses from CD8+ T cells. Furthermore, in vivo elimination of uric acid inhibits the immune response to antigens associated with dead and dying cells, but that is not the case when antigens are presented by activated dendritic cells.