Widespread intradermal accumulation of mononuclear leukocytes in lepromatous leprosy patients treated systemically with recombinant interferon gamma.

Abstract

Intradermal administration of recombinant interferon gamma (rIFN-gamma) to lepromatous leprosy patients has converted the local histology toward a tuberculoid pattern. However, such changes have been confined to the site of injection. In contrast, in the present study, marked, intradermal accumulation of CD3+, CD4+, CD8+, and CD1a+ T cells and Leu-M5+ mononuclear phagocytes was induced at a distance from the sites of administration, in a dose-dependent manner, by 10 daily intramuscular injections of 10-30 micrograms rIFN-gamma/m2. Mononuclear cell infiltration began within 3 d of onset of rIFN-gamma therapy and persisted at least 8 wk. Intramuscular administration of rIFN-gamma to lepromatous patients receiving concurrent chemotherapy can safely induce widespread histologic features of an upgrading reaction.

The role of cytokines in mycobacterial infection

“…It is possible that activated peripheral monocytes increased the clearance of dead bacteria within the lesion. In more recent studies, administration of recombinant IFN-,y in sites distant from the lepromatous lesion appear to confirm the beneficial effect of the cytokine [28]. Marked intralesional accumulation of CD3 +, CD4 +, CD8 + and CDa + T cells was observed with a dose of 10 to 30#g of recombinant IFNT/m 2 [28], converting the lepromatous lesion into a tuberculoid lesion.…”

An In Vitro Model for the Lepromatous Leprosy Granuloma: Fate ofMycobacterium lepraefrom Target Macrophages after Interaction with Normal and Activated Effector Macrophages

“…Enhancement of CMI and upgrading of clinical and histopathological classification has been attempted in borderline lepromatous and LL patients via cytokine immunotherapy. Upon injection of IFN-␥ or IL-2 into leprosy lesions, a marked cellular infiltration occurred (23,24,40), and the bacillary index, a measure of M. leprae burden, was reported to markedly decrease (41). Thus, treatment of lesions with Th1 cytokines apparently evoked a CMI response, but the effect was transient; the specific unresponsiveness to M. leprae Ags characteristic of multibacillary disease was not reversed.…”

“…First, numerous tumor models have shown that M can act as killer cells and attack abnormal cells (17)(18)(19)(20)(21)(22). Second, immunotherapy with Th1-type cytokines in LL patients demonstrated upgrading of clinical disease in the absence of specific T cell-mediated immunity (23,24).…”

Clinical Efficacy of and Immunologic Alterations Caused by Interferon g Therapy for Alveolar Echinococcosis

“…Bolus therapy with rIFN-ga (Polyferon, Bioferon, Laupfor the in vivo application of recombinant IFN-g (rIFN-g) therapy for patients with infectious diseases [4]. Systemic or heim, Germany) was administered following a previously described protocol [6]; the dose was 50 mg for the first day and local therapy with rIFN-g was found to be partially effective for leishmaniasis [5,6] and leprosy [7]. Furthermore, data from 100 mg for two consecutive days.…”