Adjuvant interferon gamma in patients with pulmonary atypical Mycobacteriosis: A randomized, double-blind, placebo-controlled study

Abstract

BackgroundHigh antibiotic resistance is described in atypical Mycobacteriosis, mainly by Mycobacterium avium complex (MAC).MethodsA 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 × 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.ResultsEighteen 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.ConclusionThese 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.Trial registrationCurrent Controlled Trials ISRCTN70900209.

Gamma Interferon Signaling in Macrophage Lineage Cells Regulates Central Nervous System Inflammation and Chemokine Production

“…These observations are intriguing given the purported role of IFN-␥ in the pathogenesis of several diseases, such as multiple sclerosis, sepsis, human immunodeficiency virus-associated dementia, and Alzheimer's (14,19,32,79,81). The results of the present study can lend insight into results from current clinical trials involving the administration of IFN-␥ as adjuvant therapy (49) and possibly the design of future trials involving IFN-␥ blockade. The present study also provides a basis for further investigation of the effects of IFN-␥ in immunopathology and neuroimmunology, as well as the effects of IFN-␥ on infection-induced anorexia, all of which may have significant implications in the development of therapies for neuroinflammatory and immune-mediated diseases.…”

British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD)

“…In a randomised controlled trial performed in Cuba, 32 patients with predominantly MAC-pulmonary disease were randomised to receive intramuscular interferon gamma (1×10 6 IU) or placebo daily for 4 weeks, followed by thrice weekly administration for up to 6 months, in addition to a standardised antibiotic regimen 291. The primary composite endpoint (incorporating an improvement in symptoms, radiology and microbiology) was achieved by 13/18 (72%) participants receiving Interferon gamma versus 5/14 (36%) receiving placebo (p=0.037) after 6 months of treatment and the improvement was maintained for 12 months following treatment cessation.…”

IFN-γ differentially regulates subsets of Gr-1+CD11b+ myeloid cells in chronic inflammation

“…Thus, a better understanding of the mechanisms involved in the delicate balance between over-reactive inflammation and immunosuppression would identify novel potential therapeutic targets. IFN-␥ is widely used to treat inflammatory diseases, such as tuberculosis and hepatitis (Katayama et al, 2001;Milanes-Virelles et al, 2008). However, the precise mechanisms through which IFN-␥ benefits chronic disease treatment remain poorly known.…”

“…Recombinant protein IFN-␥-1b (Actimmune), has been widely used to treat chronic diseases, including cancer (Matsushita et al, 2006), tuberculosis (Milanes-Virelles et al, 2008), hepatitis (Katayama et al, 2001), chronic granulamotous disease (Marciano et al, 2004) and etc. IFN-␥ contributes to the regulation of T cell homeostasis and innate immune cells including dendritic cells (DC) and macrophages (Young and Bream, 2007).…”