INFLAMMATION OF THE RAT PROSTATE EVOKES RELEASE OF MACROPHAGE MIGRATION INHIBITORY FACTOR IN THE BLADDER: EVIDENCE FOR A VISCEROVISCERAL REFLEX

Abstract

Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, is found in preformed stores in bladder epithelium. We examined the effects of prostatic inflammation on micturition frequency, bladder histology and bladder MIF content as a model in which to study viscerovisceral reflexes mediating pelvic visceral inflammation. Cystometry was performed in urethane anesthetized male rats. Formalin or saline was injected into the ventral lobe of the prostate to induce inflammation. Cystometry continued 1 hour after injection. The bladder, ventral lobes of the prostates and lumbosacral spinal cord were then removed, and protein levels and gene expression of MIF, cyclooxygenase-2 (COX-2) and nerve growth factor (NGF) were examined. Edema was verified histologically in the bladder and prostate. Intraprostatic formalin produced almost immediate bladder hyperreflexia, which was maintained during the observation period. Bladder edema was noted during histological examination. Bladder MIF protein amounts decreased, while COX-2 and NGF increased after prostatic injection. Bladder MIF, COX-2 and NGF mRNA increased. In the lumbosacral spinal cord protein and mRNA amounts increased for all factors examined in animals that received intraprostatic formalin. No changes were observed in the cervical cord. Rats injected with formalin mixed with dye showed restriction of the dye to the prostate. A viscerovisceral reflex in the rat, probably mediated by the lumbosacral spinal cord, produced bladder hyperreflexia and bladder edema, and evoked MIF release from the bladder and the induction of other inflammatory mediators. This supports our hypothesis that MIF is involved in neurogenic inflammation in the pelvic viscera and it may represent an interesting therapeutic target.