Adjuvant interferon gamma in patients with drug - Resistant pulmonary tuberculosis: A pilot study

Benéfico Jurídico Hospital, Havana, Cuba. <>
BMC Infectious Diseases (Impact Factor: 2.61). 11/2004; 4(1):44. DOI: 10.1186/1471-2334-4-44
Source: PubMed


Tuberculosis (TB) is increasing in the world and drug-resistant (DR) disease beckons new treatments.
To evaluate the action of interferon (IFN) gamma as immunoadjuvant to chemotherapy on pulmonary DR-TB patients, a pilot, open label clinical trial was carried out in the Cuban reference ward for the management of this disease. The eight subjects existing in the country at the moment received, as in-patients, 1 x 10(6) IU of recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to the indicated chemotherapy, according to their antibiograms and WHO guidelines. Sputum samples collection for direct smear observation and culture as well as routine clinical and thorax radiography assessments were done monthly.
Sputum smears and cultures became negative for acid-fast-bacilli before three months of treatment in all patients. Lesion size was reduced at the end of 6 months treatment; the lesions disappeared in one case. Clinical improvement was also evident; body mass index increased in general. Interferon gamma was well tolerated. Few adverse events were registered, mostly mild; fever and arthralgias prevailed.
These data suggest that IFN gamma is useful and well tolerated as adjunctive therapy in patients with DR-TB. Further controlled clinical trials are encouraged.

Download full-text


Available from: Pedro Antonio Lopez-Saura, Sep 30, 2015
27 Reads
  • Source
    • "They concluded that recombinant IFN-g in combination with directly observed therapy can reduce inflammatory cytokines at the site of infection, improve bacterial clearance from the sputum, and improve constitutional symptoms of tuberculosis disease (Dawson et al., 2009). However, earlier studies did not show a long-term microbiological effect, indicating that additional studies are needed to determine the durability and long-term impact of IFN-g therapy (Giosue et al., 2000; Koh et al., 2004; Suarez-Mendez et al., 2004). Interleukin 2 (IL-2) is another cytokine evaluated for its immunotherapeutic potential. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Granuloma formation represents a pivotal point during human infection with Mycobacterium tuberculosis, for this structure may limit mycobacterial spread and prevent active disease, while at the same time allow for the survival and persistence of viable mycobacteria within the host. The current therapeutic regimens for treating tuberculosis disease have proven effective in developing countries. However, in countries with large populations, limited access to health care, and high incidence of HIV co-infection, tuberculosis disease continues to represent a major global health emergency. Particularly, the emergence of extensively and multi-drug-resistant forms of tuberculosis underscores the need develop new treatment strategies. Recent mechanistic studies have identified bacterial virulence mechanisms that subvert host responses and lead to an inappropriate upregulation of host factors such as tumour necrosis factor-alpha (TNF-alpha) and matrix metalloproteinases (MMPs). Paradoxically, then, part of the mycobacterial virulence programme may be to promote granuloma development and maturation. These observations suggest that together with appropriate anti-microbials host-based therapeutics directed at TNF-alpha and MMP inhibition may counteract the microbial subterfuge, reduce the pro-granulomatous response, and offer an enhanced therapeutic effect. Host-directed therapy that alters the immune response may offer an alternative approach towards reducing treatment duration, the risk of anti-microbial resistance and improving patient outcome.
    Cellular Microbiology 03/2010; 12(3):301-9. DOI:10.1111/j.1462-5822.2009.01424.x · 4.92 Impact Factor
  • Source
    • "This probably explains our finding that only nebulized rIFN-γ1b and not subcutaneous rIFN-γ1b was successful in clearing the sputum of Mtb and reducing the spontaneous release of inflammatory cytokines in 24 hour BAL supernatants. A pilot study of intramuscular rIFN-γ plus second-line anti-TB drugs over a 6-month period in 8 MDR-TB patients from Cuba showed sputum conversion over 1–3 months and marked improvement of radiographic abnormalities [17]. Giosue and colleagues nebulized IFN-α, a type I interferon, for 2 months as an adjunct in a randomized controlled clinical trial in 20 drug sensitive tuberculosis patients [18]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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. 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. NCT00201123.
    PLoS ONE 09/2009; 4(9):e6984. DOI:10.1371/journal.pone.0006984 · 3.23 Impact Factor
  • Source
    • "To name a few examples, IL-2 has proved useful, usually in combination with standard chemotherapeutics or other cytokines such as IFN-a2b, in treatment of malignancies [10] [11] and viral infections [12]. IFN-c has beneficial effects in many models of infections caused by viruses, bacteria, protozoa, helminths, and fungi [13], is useful as adjuvant therapy in tuberculosis patients that have resistance to standard chemotherapy [14] [15], and it seems to be an alternative for patients with hyper- IgG states such as atopic dermatitis who do not respond to other forms of treatment [16] [17]. Due to the huge complexity of immune system, it is an uneasy task to reach generally accepted criteria how to search for immunobiological activity of compounds. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Activation of inducible nitric oxide (NO) synthase (iNOS) and resulting high-output NO release is known to depend on the action of cytokines. We investigated in vitro production of NO by resident peritoneal macrophages from mice and rats, and secretion of cytokines by these cells as well as by human peripheral blood mononuclear cells (PBMC). The cells were cultured in the presence of a selected group of acyclic nucleoside phosphonates that have previously been shown to possess immunobiological potential. Several of the compounds enhanced production of NO in animal macrophages. This activity was associated with stimulatory effects on secretion of cytokines such as TNF-alpha in all mouse and rat macrophages and human PBMC, and IL-10 in mouse and human cells. Statistically highly significant correlation between the range of NO biosynthesis in rodent cells and extent of cytokine stimulation in human PBMC has been observed. It is suggested that the NO assay may be regarded as an efficient, economical and relatively reliable tool in primary screening for intrinsic immunostimulatory activity of compounds in human cell system, at least from the point of view of cytokine secretion.
    Nitric Oxide 11/2007; 17(3-4):160-9. DOI:10.1016/j.niox.2007.06.006 · 3.52 Impact Factor
Show more