Immunological consequences of three doses of heat-killed Mycobacterium vaccae in the immunotherapy of tuberculosis.
We report the first study of triple-dose immunotherapy with heat-killed Mycobacterium vaccae (SRL 172) combined with short-course, directly observed chemotherapy in newly diagnosed pulmonary tuberculosis patients. The study was carried out in Rosario, Argentina, where single-dose immunotherapy with M. vaccae has previously been shown effective. Twenty-two HIV seronegative patients, sputum-positive for tubercle bacilli, entered a randomised and partly blinded trial. Twelve patients received injections of SRL 172 and 10 patients received placebo on days 1, 30 and 60 of chemotherapy. All patients were followed up clinically, by sputum bacteriology, chest radiography and haematology. Patients receiving SRL 172 showed faster and more complete clinical improvement, accelerated disappearance of bacilli from sputum, better radiological clearance and a more rapid fall in ESR, than did those receiving placebo. Follow-up continued for a year after therapy and no patient failed treatment or relapsed. Special investigations included longitudinal assessments of respiratory bursts and expression of CD11b on separated polymorphonuclear and mononuclear leukocytes. Tumour necrosis factor alpha (TNF-alpha) was measured in the supernates of cultured cells and both TNF-alpha and interleukin-4 (IL-4) were measured in serum samples. Immunotherapy recipients showed a significantly faster return towards normal values in all the immunological parameters, than did placebo recipients. The results are consistent with a regulatory activity on cellular immunity, reducing the influence of Th2 and enhancing Th1 to the benefit of the patients. This could allow a reduced period of chemotherapy without loss of efficacy and help to prevent the development of multi-drug resistance.
Dlugovitzky
Diana
D
Catedra de Microbiologia, Virologia y Parasitologia, Facultad de Ciencias Medicas, Universidad Nacional de Rosario, Santa Fe 3100, 2000 Rosario, Argentina.
Fiorenza
Gladys
G
Farroni
Miguel
M
Bogue
Christine
C
Stanford
Cynthia
C
Stanford
John
J
D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001428:Bacterial Vaccines / Q000008:administration & dosage*; D015415:Biomarkers / Q000032:analysis; D003131:Combined Modality Therapy; D016207:Cytokines / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009161:Mycobacterium / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011859:Radiography; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage*
D000995:Antitubercular Agents; D001428:Bacterial Vaccines; D015415:Biomarkers; D016207:Cytokines; D014613:Vaccines, Attenuated; C451081:SRL172