Interstitial cystitis: a neuroimmunoendocrine disorder.
Theoharides TC, Pang X, Letourneau R, Sant GR
Ann N.Y. Acad Sci 1988 May 1; 840: 619-634
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Interstitial cystitis (IC) is a sterile bladder condition occurringprimarily in females. It is characterized by frequency, nocturia,and suprapubic pain. ICsymptoms are exacerbated duringovulation and under stress, thus implicatingneurohormonalprocesses. The most prevalent theories to explainthepathophysiology of IC appear to be altered bladder lining andincreased number of activated bladder mast cells. A defectivebladder glycosaminoglycan (GAG)layer could allow penetrationof allergic triggers, as well as chemicals, food preservatives,drugs, toxins, and adherent bacteria, all of which can activatebladder mast cells. Vasoactive, nociceptive, and proinflammatorymolecules released can lead to immune cell infiltration and cansensitize neurons to secrete neurotransmitters or neuropeptidesthat can further activate mast cells.Mast cell-derived proteasescan directly cause tissue damage, and it is noteworthy that urinetryptase is elevated in IC. Bladder mast cells are located close toneuronal processes, which are increased in IC, and they can beactivated in situ by acetylcholine (ACh) and substance P (SP).Such activation is augmented by estradiol, which acquiressignificance in view of the fact that human bladder mast cellsexpress estrogen receptors, but few progesterone receptors,which may explain the worsening of IC symptoms duringovulation. Finally, acute psychological stress in rats leads tomast cell activation that can be reduced by depletion of SP orneutralization of peripheral immunecorticotropin-releasinghormone (CRH). These findings suggest that IC could be a syndrome with neural, immune, and endocrine components, inwhich activated mast cells play a central role.
Publication Types:ReviewReview, tutorial
PMID: 9629289′, ‘PDF Version for Download
Research from Dr. Theoharides