title: Prevention of the post-chemotherapy relapse of tuberculous infection by combined immunotherapy.
abstract: 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 4weeks of non-sterilising treatment with isoniazid and rifampicin. The CIT regimen, represented by recombinant IFNgamma, anti-alpha 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.
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Università di Palermo, Corso Tukory, Palermo, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Buccheri
authors.forename: Rajko
authors.initials: R
authors.lastname: Reljic
authors.forename: Nadia
authors.initials: N
authors.lastname: Caccamo
authors.forename: Serena
authors.initials: S
authors.lastname: Meraviglia
authors.forename: Juraj
authors.initials: J
authors.lastname: Ivanyi
authors.forename: Alfredo
authors.initials: A
authors.lastname: Salerno
authors.forename: Francesco
authors.initials: F
authors.lastname: Dieli
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D003131:Combined Modality Therapy; D007070:Immunoglobulin A / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000627:therapeutic use; D015847:Interleukin-4 / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009169:Mycobacterium tuberculosis; D011994:Recombinant Proteins; D012008:Recurrence; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000628:therapy; D038201:alpha-Crystallins / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D000995:Antitubercular Agents; D007070:Immunoglobulin A; D011994:Recombinant Proteins; D038201:alpha-Crystallins; C500452:alpha-crystallin 2, Mycobacterium tuberculosis; D015847:Interleukin-4; D007371:Interferon-gamma