Immunomodulation with Recombinant Interferon-γ1b in Pulmonary Tuberculosis

Abstract

BackgroundCurrent treatment regimens for pulmonary tuberculosis require at least 6 months of therapy. Immune adjuvant therapy with recombinant interferon-γ1b (rIFN-γb) may reduce pulmonary inflammation and reduce the period of infectivity by promoting earlier sputum clearance.Methodology/Principal FindingsWe performed a randomized, controlled clinical trial of directly observed therapy (DOTS) versus DOTS supplemented with nebulized or subcutaneously administered rIFN-γ1b 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-1β, IL-6, IL-8, and IL-10 in 24-hour BAL supernatants only in the nebulized rIFN-γ1b group from baseline to week 16. Both rIFN-γ1b 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-γ1b adjuvant group compared to DOTS or DOTS with subcutaneous rIFN-γ1b. In addition, there was significant reduction in the prevalence of fever, wheeze, and night sweats at 4 weeks among patients receiving rFN-γ1b versus DOTS alone.ConclusionRecombinant interferon-γ1b 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.Trial RegistrationClinicalTrials.gov NCT00201123

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

“…152 On the other hand, TNF-α inhibition destabilizes granulomas, reactivates Mtb bacilli and increases the risk of TB disease. 153 IFN-γ is important to protective anti-TB immunity and administration has nominal benefit in drug-sensitive, 154 and drug-resistant TB. 155 Although several HDTs show promise in pre-clinical studies, insufficient information is …”

α-Galactosylceramide as a Therapeutic Agent for PulmonaryMycobacterium tuberculosisInfection

“…Although IFN-g, IL-2, IL-12, and thalidomide have been tried as immune modulators in patients with pulmonary TB, the results of experimental studies and clinical trials have been only moderately encouraging (33)(34)(35)(36)(37). Although many clinical studies using IFN-g, IL-12, and thalidomide have demonstrated the potential of these agents to enhance immune responses to infection (38,39), a clinical response has been fleeting.…”

Treatment of tuberculosis: update 2010

“…Table 6 depicts the results of a number of preliminary studies regarding the use of cytokines (especially IFN-c) [246][247][248][249][250][251] and Mycobacterium vaccae (NCTC 11659) [252], an avirulent vaccine from a nontuberculous mycobacterial species, in the management of MDR tuberculosis. In a more recent study, nebulised IFN-c1b adjuvant therapy was also found to improve constitutional symptoms, reduce inflammatory cytokines in bronchoalveolar lavage and improve clearance of acid-fast bacilli from sputum in cavitary pulmonary tuberculosis [253]. While the results from some of these studies are encouraging, the limited number of enrolled patients, alongside often uncontrolled experimental designs, leaves great uncertainty regarding the definitive role of these cytokines and allied forms of immunotherapy in tuberculosis treatment.…”