A Proposed Mechanism of the Inflammatory Attacks in Familial Mediterranean Fever

To the Editor. — Multiple and varied mechanisms have been proposed to underlie the pathogenesis of the acute febrile attacks of recurrent hereditarypolyserositis, also called familial Mediterranean fever (FMF). However, the pathogenesis of FMF has, thus far, remained enigmatic. 1 We have recently examined whether the lymphokine tumor necrosis factor (TNF), which has many inflammatory activities, 2 may be involved in mediating the acute attacks of FMF. Although plasma TNF was not increased in patients with FMF, we found that the capacity of patients' peripheral blood mononuclear cells to produce TNF in response to an inducer was severely diminished in the acute phase, increasing by about fivefold in asymptomatic patients with FMF, to levels significantly over those of healthy control subjects. 3 This was most probably due to "exhaustion" of the cells following an already massive release of TNF, which could not be demonstrated due to a short plasma