Significance of Neutrophil Activation in Reactional Lepromatous Leprosy: Effects of Thalidomide in vivo and in vitro. Activation in Adjuvant Disease

Abstract

A proportion of circulating neutrophils is able to reduce nitroblue tetrazolium (NBT) in vitro. Such cells show blue formazan precipitates in their cytoplasm (FP cells). The proportion of FP cells is raised in many bacterial infections because of increased oxido-reductive activity (activation). This may also be induced in vitro by incubation with endo-toxin. We have previously reported that, while in lepromatous leprosy (LL) there was no activation, a significant elevation in proportion of FP cells took place in reactional lepromatous leprosy (RLL). RLL is reported to be a form of immune complex disease, therefore, neutrophils would be involved in tissue damage. Signs and symptoms of RLL are dramatically improved by thalidomide. We have now studied neutrophil activation in patients with RLL just before and during treatment with thalidomide. Clinical improvement produced by this drug took place before lowering the proportion of FP cells. Concomitant infectious processes induced activation even if patients were under thalidomide treatment. Thalidomide, tested in vitro, did not affect spontaneous reduction of NBT by neutrophils, nor did it block endotoxin-induced activation. The therapeutic effect of thalidomide is not related to properties inhibiting neutrophil activation. RLL has features that resemble those of adjuvant disease (ADJ). The latter is induced in the rat by injecting killed mycobacteria suspended in an oily vehicle. Inflammatory lesions, owing mainly to delayed hypersensitivity, appear in joints, skin and eyes. Thalidomide has suppressive properties concerning the signs of ADJ. We now studied neutrophil activation in rats of two strains: one susceptible to ADJ and the other refractory. Neutrophils from rats of both strains were able to become activated by in vitro incubation with endotoxin, latex particles and Staphylococcus aureus suspensions. After injection of mycobacteria, rats from the refractory strain showed little or no ADJ or neutrophil activation, despite the presence of inflammation at the injected site and gross enlargement of draining lymph nodes. Susceptible rats had a very intense ADJ. There was also a significant increase in proportion of FP cells, but this took place shortly after injection of mycobacteria and before signs of ADJ or acme of local inflammation had taken place. Activation disappeared by the time that ADJ became apparent. Significant neutrophil activation did not occur when susceptible rats received the oily vehicle alone. Our findings do not support the hypothesis that tissue damage in RLL is due solely to neutrophil action by a mechanism similar to that of immune complex disease. Activation may be in RLL as in ADJ a specific phenomenon induced by a lymphokine.