6533b85ffe1ef96bd12c11e6

RESEARCH PRODUCT

Prevention of the post-chemotherapy relapse of tuberculous infection by combined immunotherapy

Alfredo SalernoSimona BuccheriSerena MeravigliaFrancesco DieliNadia CaccamoRajko ReljicJuraj Ivanyi

subject

MaleMicrobiology (medical)TuberculosisTuberculosiAntibodiemedicine.medical_treatmentImmunologyAntitubercular AgentsColony Count MicrobialMicrobiologyAntibodiesMycobacterium tuberculosisInterferon-gammaMiceAdjuvants ImmunologicRecurrencemedicineAnimalsalpha-CrystallinsRelapseTuberculosis PulmonaryCytokineMice Inbred BALB CMice Inbred C3HChemotherapyLungbiologybusiness.industryTuberculosis; Cytokines; Antibodies; Immunotherapy; RelapseIsoniazidMycobacterium tuberculosisImmunotherapybiology.organism_classificationmedicine.diseaseCombined Modality TherapyRecombinant ProteinsImmunoglobulin AMice Inbred C57BLRegimenInfectious Diseasesmedicine.anatomical_structureModels AnimalImmunologyInterleukin-4ImmunotherapybusinessRifampicinmedicine.drug

description

Summary We report that a recently developed combined immunotherapy (CIT) has the capacity to prevent a spontaneous relapse of replicating Mycobacterium tuberculosis bacilli in the lungs of BALB/c, C57Bl/6 or C3H/HeJ strains of mice, following 4 weeks of non-sterilising treatment with isoniazid and rifampicin. The CIT regimen, represented by recombinant IFNγ, anti-α crystalline monoclonal IgA antibody and IL-4 neutralizing polyclonal antibody, reduced the 8-week relapse of viable bacterial counts in the lungs most significantly, when CIT was inoculated during the 5th week post infection, i.e. during the 3rd week of chemotherapy. Although CIT enhanced lung granuloma area, nitric oxide, cytokine and chemokine levels in lung washings significantly, these could not be directly associated with the beneficial effect of CIT on the degree of relapse in the lungs. These results represent a proof-of-principle, that the described CIT, when combined with chemotherapy, could have potential for future development of a shorter regimen of tuberculosis treatment.

https://doi.org/10.1016/j.tube.2008.09.001