title: Adjuvant interferon gamma in patients with pulmonary atypical Mycobacteriosis: a randomized, double-blind, placebo-controlled study.
abstract: BACKGROUND
  High antibiotic resistance is described in atypical Mycobacteriosis, mainly by Mycobacterium avium complex (MAC).
  
  
  METHODS
  A randomized, double-blind, placebo-controlled clinical trial was carried out in two hospitals to evaluate the effect of interferon (IFN) gamma as immunoadjuvant to chemotherapy on patients with atypical mycobacteria lung disease. Patients received placebo or 1 x 106 IU recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to daily oral azithromycin, ciprofloxacin, ethambutol and rifampin. Sputum samples collection for direct smear observation and culture as well as clinical and thorax radiography assessments were done during treatment and one year after. Cytokines and oxidative stress determinations were carried out in peripheral blood before and after treatment.
  
  
  RESULTS
  Eighteen patients were included in the IFN group and 14 received placebo. Groups were homogeneous at entry; average age was 60 years, 75% men, 84% white; MAC infection prevailed (94%). At the end of treatment, 72% of patients treated with IFN gamma were evaluated as complete responders, but only 36% in the placebo group. The difference was maintained during follow-up. A more rapid complete response was obtained in the IFN group (5 months before), with a significantly earlier improvement in respiratory symptoms and pulmonary lesions reduction. Disease-related deaths were 35.7% of the patients in the placebo group and only 11.1% in the IFN group. Three patients in the IFN group normalized their globular sedimentation rate values. Although differences in bacteriology were not significant during the treatment period, some patients in the placebo group converted again to positive during follow-up. Significant increments in serum TGF-beta and advanced oxidation protein products were observed in the placebo group but not among IFN receiving patients. Treatments were well tolerated. Flu-like symptoms predominated in the IFN gamma group. No severe events were recorded.
  
  
  CONCLUSIONS
  These data suggest that IFN gamma is useful and well tolerated as adjuvant therapy in patients with pulmonary atypical Mycobacteriosis, predominantly MAC. Further wider clinical trials are encouraged.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN70900209.
authors.affiliation: Center for Biological Research, Clinical Trials Division, Havana, Cuba. mariateresam@infomed.sld.cu
authors.forename: María T
authors.initials: MT
authors.lastname: Milanés-Virelles
authors.forename: Idrian
authors.initials: I
authors.lastname: García-García
authors.forename: Yamilet
authors.initials: Y
authors.lastname: Santos-Herrera
authors.forename: Magalys
authors.initials: M
authors.lastname: Valdés-Quintana
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Valenzuela-Silva
authors.forename: Gaspar
authors.initials: G
authors.lastname: Jiménez-Madrigal
authors.forename: Thelvia I
authors.initials: TI
authors.lastname: Ramos-Gómez
authors.forename: Iraldo
authors.initials: I
authors.lastname: Bello-Rivero
authors.forename: Norma
authors.initials: N
authors.lastname: Fernández-Olivera
authors.forename: Reinaldo B
authors.initials: RB
authors.lastname: Sánchez-de la Osa
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodríguez-Acosta
authors.forename: Lidia
authors.initials: L
authors.lastname: González-Méndez
authors.forename: Gregorio
authors.initials: G
authors.lastname: Martínez-Sánchez
authors.forename: Pedro A
authors.initials: PA
authors.lastname: López-Saura
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000368:Aged; D003462:Cuba; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D004358:Drug Therapy; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D008168:Lung / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009165:Mycobacterium Infections, Nontuberculous / Q000188:drug therapy / Q000276:immunology*; D015269:Mycobacterium avium Complex / Q000276:immunology; D018384:Oxidative Stress; D011994:Recombinant Proteins; D013183:Sputum / Q000382:microbiology
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D011994:Recombinant Proteins; D007371:Interferon-gamma