Catecholamine metabolism in recurrent hereditary polyserositis. Pathogenesis of acute inflammation: the retention—leakage hypothesis

Abstract

Recurrent hereditary polyserositis (RHP), also known as familial Mediterranean fever, is a genetically-determined disease characterized by paroxysmal attacks of peritonitis, pleuritis, arthritis or inflammation of other serous membranes. We have previously suggested that the pathogenesis of this disease seems to be related to abnormal catecholamine metabolism. This study compares the plasma and urine catecholamine profile in patients with RHP during different clinical states to that in controls. In RHP there were lower plasma and higher urine dopamine levels in the asymptomatic state and during attacks, while norepinephrine levels remain unchanged. However, plasma epinephrine was significantly lower in the asymptomatic state but markedly higher during attacks. The urine epinephrine values in both situations were similar but significantly lower than in controls, suggesting abnormal renal excretion of epinephrine. The urine metanephrine was markedly elevated in the asymptomatic state compared to controls, but remained unchanged during the attacks, again suggesting defective renal clearance of metanephrine. Metaraminol infusion, which induces attacks in RHP patients, was associated with an increase in plasma dopamine and epinephrine (but not norepinephrine); yet the urinary levels of dopamine, epinephrine and metanephrine remained the same, confirming the dissociation between the plasma and urinary levels of these catecholamines, probably due to abnormalities in the renal clearance mechanism. We postulate that this dissociation leads to retention of these amines in the plasma which may subsequently leak through the serous membranes (the target organs) and incite an acute inflammatory process. Cotchicine, the only known drug that protects against disease attacks, reduces the plasma levels of these amines, and thus may act by preventing retention that leads to leakage and subsequent inflammation. catecholamine/polyserositis/colchicine