Variable major lipoprotein is a principal TNF-inducing factor of louse-borne relapsing fever

Massive release of tumor necrosis factor is responsible for the potentially fatal jarisch-Herxheimer reaction that follows antibiotic treatment of rel apsing fever due to Borrelia recurrentis. We have undertaken the quantitati ve purification of the components of B. recurrentis that stimulate human mo nocytes to produce tumor necrosis factor. We show that the predominant fact or inducing tumor necrosis factor is a variable lipoprotein homologous to t he variable major protein of B. hermsii. We found antibodies to different f orms of variable major protein in two patients with louse-borne relapsing f ever. The three purified variable major proteins studied here differ in the ir ability to induce tumor necrosis factor production, which may partly exp lain the variable clinical severity of borrelial infection. These results m ay be of considerable relevance for the pathogenesis of Lyme disease and ot her forms of human borreliosis.