Immunomodulation with recombinant interferon-gamma1b in pulmonary tuberculosis.
BACKGROUND
Current treatment regimens for pulmonary tuberculosis require at least 6 months of therapy. Immune adjuvant therapy with recombinant interferon-gamma1b (rIFN-gammab) may reduce pulmonary inflammation and reduce the period of infectivity by promoting earlier sputum clearance.


RESULTS
We performed a randomized, controlled clinical trial of directly observed therapy (DOTS) versus DOTS supplemented with nebulized or subcutaneously administered rIFN-gamma1b over 4 months to 89 patients with cavitary pulmonary tuberculosis. Bronchoalveolar lavage (BAL) and blood were sampled at 0 and 4 months. There was a significant decline in levels of inflammatory cytokines IL-1beta, IL-6, IL-8, and IL-10 in 24-hour BAL supernatants only in the nebulized rIFN-gamma1b group from baseline to week 16. Both rIFN-gamma1b groups showed significant 3-fold increases in CD4+ lymphocyte response to PPD at 4 weeks. There was a significant (p = 0.03) difference in the rate of clearance of Mtb from the sputum smear at 4 weeks for the nebulized rIFN-gamma1b adjuvant group compared to DOTS or DOTS with subcutaneous rIFN-gamma1b. In addition, there was significant reduction in the prevalence of fever, wheeze, and night sweats at 4 weeks among patients receiving rFN-gamma1b versus DOTS alone.


CONCLUSIONS
Recombinant interferon-gamma1b adjuvant therapy plus DOTS in cavitary pulmonary tuberculosis can reduce inflammatory cytokines at the site of disease, improve clearance of Mtb from the sputum, and improve constitutional symptoms.


BACKGROUND
ClinicalTrials.gov NCT00201123.
Dawson
Rod
R
Division of Pulmonology, Department of Medicine, Health Sciences Faculty, University of Cape Town, Cape Town, South Africa.
Condos
Rany
R
Tse
Doris
D
Huie
Maryann L
ML
Ress
Stanley
S
Tseng
Chi-Hong
CH
Brauns
Clint
C
Weiden
Michael
M
Hoshino
Yoshihiko
Y
Bateman
Eric
E
Rom
William N
WN
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D056747:Immunomodulation; D007167:Immunotherapy / Q000379:methods*; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use; D013183:Sputum / Q000276:immunology; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy*
D016207:Cytokines; D011994:Recombinant Proteins; D007371:Interferon-gamma