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2000
Volume 25, Issue 6
  • ISSN: 1871-5265
  • E-ISSN: 2212-3989

Abstract

Background

In this article, we present the results of a multicenter clinical trial of IFN-γ in patients with drug-susceptible and drug-resistant pulmonary Tuberculosis (TB) in routine clinical practice.

Objective

This study aimed to confirm the efficacy and safety of IFN-γ administered to patients with TB.

Methods

All patients were diagnosed with TB after being tested by bacterioscopic and molecular genetic methods and had no contraindications to standard chemotherapy.

Results

Recombinant human IFN-γ proved high efficacy in multi-center clinical trial in routine TB practice.

Conclusion

The results show that IFN-γ is efficient and safe in the treatment of pulmonary tuberculosis.

Clinical Trial Registration #

NCT06118619.

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/content/journals/iddt/10.2174/0118715265329137250102103507
2025-01-27
2025-11-05
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References

  1. KhanT.A. MazharH. SalehaS. TipuH.N. MuhammadN. AbbasM.N. Interferon-gamma improves macrophages function against M. tuberculosis in multidrug-resistant tuberculosis patients.Chemother. Res. Pract.201620161610.1155/2016/7295390 27478636
    [Google Scholar]
  2. SharmaD. SharmaS. SharmaJ. Potential strategies for the management of drug-resistant tuberculosis.J. Glob. Antimicrob. Resist.20202221021410.1016/j.jgar.2020.02.029 32169684
    [Google Scholar]
  3. SerebryakovaV.A. Reactivity of peripheral blood lymphocytes in pulmonary tuberculosis. Abstract of a thesis for a degree of candidate of medical sciences2006
    [Google Scholar]
  4. GorlovaE.E. Immunity pathology in tuberculosis.Bull Physiol Pathol Resp2010353744
    [Google Scholar]
  5. MaslennikovA.A. ObolonkovaN.I. Efficiency of Ingaron in the treatment of patients with destructive pulmonary bacteriologically proven tuberculosis.MedPharm Ser2016210.18413/2313‑8955‑2016‑2‑1‑10‑16
    [Google Scholar]
  6. GhanaviJ. FarniaP. FarniaP. VelayatiA.A. The role of interferon-gamma and interferon-gamma receptor in tuberculosis and nontuberculous mycobacterial infections.Int. J. Mycobacteriol.202110434935710.4103/ijmy.ijmy_186_21 34916451
    [Google Scholar]
  7. BalasaniantsG.S. RuzanovD.Y. Immunotherapeutic role of interferon-γ at tuberculosis.Immunologiya202243334335110.33029/0206‑4952‑2022‑43‑3‑343‑351[in Russian].
    [Google Scholar]
  8. BrooksB.M. HartC.A. ColemanJ.W. Differential effects of β-lactams on human IFN-γ activity.J. Antimicrob. Chemother.20055661122112510.1093/jac/dki373 16239287
    [Google Scholar]
  9. PerelmanM.I. Phthisiology: National Guidelines.MoscowGEOTAR-Media2007
    [Google Scholar]
  10. BeharS.M. CarpenterS.M. BootyM.G. BarberD.L. JayaramanP. Orchestration of pulmonary T cell immunity during Mycobacterium tuberculosis infection: Immunity interruptus.Semin. Immunol.201426655957710.1016/j.smim.2014.09.003 25311810
    [Google Scholar]
  11. ManeaA. ManeaS.A. GanA.M. Human monocytes and macrophages express NADPH oxidase 5; a potential source of reactive oxygen species in atherosclerosis.Biochem. Biophys. Res. Commun.2015461117217910.1016/j.bbrc.2015.04.021 25871798
    [Google Scholar]
  12. BarberoA.M. TrottaA. GenoulaM. SLAMF1 signaling induces Mycobacterium tuberculosis uptake leading to endolysosomal maturation in human macrophages.J. Leukoc. Biol.2021109125727310.1002/JLB.4MA0820‑655RR 32991756
    [Google Scholar]
  13. NakajimaM. MatsuyamaM. KawaguchiM. Nrf2 regulates granuloma formation and macrophage activation during mycobacterium avium infection via mediating Nramp1 and HO-1 expressions.MBio2021121e01947e2010.1128/mBio.01947‑20 33563837
    [Google Scholar]
  14. LutckyA.A. ZhirkovA.A. LobzinD.Yu. Interferon-γ: biological function and application for study of cellular immune response.Z. Infektol.201574102210.22625/2072‑6732‑2015‑7‑4‑10‑22
    [Google Scholar]
  15. TebrueggeM. DuttaB. DonathS. Mycobacteria-specific cytokine responses detect tuberculosis infection and distinguish latent from active tuberculosis.Am. J. Respir. Crit. Care Med.2015192448549910.1164/rccm.201501‑0059OC 26030187
    [Google Scholar]
  16. Koval’chukL.V. Theory of inflammation in light of new data: Development of I.I Mechnikov ideas.Zh. Mikrobiol. Epidemiol. Immunobiol.200851015 19004278
    [Google Scholar]
  17. Il’inskayaI.F. Topical issues of rational interferon therapy in tuberculosis.Klinicheskaya Immunologiya Allergologiya Infectologiya201231822
    [Google Scholar]
  18. CondosR. RomW.N. SchlugerN.W. Treatment of multidrug-resistant pulmonary tuberculosis with interferon-γ via aerosol.Lancet199734990641513151510.1016/S0140‑6736(96)12273‑X 9167461
    [Google Scholar]
  19. Suárez-MéndezR. García-GarcíaI. Fernández-OliveraN. Adjuvant interferon gamma in patients with drug – Resistant pulmonary tuberculosis: A pilot study.BMC Infect. Dis.2004414410.1186/1471‑2334‑4‑44 15500691
    [Google Scholar]
  20. ParkS.K. ChoS. LeeI.H. Subcutaneously administered interferon-gamma for the treatment of multidrug-resistant pulmonary tuberculosis.Int. J. Infect. Dis.200711543444010.1016/j.ijid.2006.12.004 17321178
    [Google Scholar]
  21. RaadI. HachemR. LeedsN. SawayaR. SalemZ. AtwehS. Use of adjunctive treatment with interferon-gamma in an immunocompromised patient who had refractory multidrug-resistant tuberculosis of the brain.Clinical Infectious Diseases199622357257410.1093/clinids/22.3.572
    [Google Scholar]
  22. Tuberculosis in adults. Clinical recommendations [Klinicheskie rekomendatsii Tuberkulez u vzroslykh,]. 2022. (In Russian).
    [Google Scholar]
  23. HortelanoS. AlvarezA.M. BOSCá LISARDO. Nitric oxide induces tyrosine nitration and release of cytochrome c preceding an increase of mitochondrial transmembrane potential in macrophages.FASEB J.199913152311231710.1096/fasebj.13.15.2311 10593878
    [Google Scholar]
  24. ZhangJ. SunB. HuangY. IFN-γpromotes THP-1 cell apoptosis during early infection with Mycobacterium bovis by activating different apoptotic signaling.FEMS Immunol. Med. Microbiol.201060319119810.1111/j.1574‑695X.2010.00732.x 20875052
    [Google Scholar]
  25. ChechushkovA.V. ZenkovN.K. KozhinP.M. KolpakovaT.A. MenschikovaE.B. Autophagy in the pathogenesis of tuberculosis.Tuber. Lung Dis.2016943819
    [Google Scholar]
  26. SinghN. KansalP. AhmadZ. Antimycobacterial effect of IFNG (interferon gamma)-induced autophagy depends on HMOX1 (heme oxygenase 1)-mediated increase in intracellular calcium levels and modulation of PPP3/calcineurin-TFEB (transcription factor EB) axis.Autophagy201814612010.1080/15548627.2018.1436936 29457983
    [Google Scholar]
  27. MatsuzawaT. KimB.H. ShenoyA.R. KamitaniS. MiyakeM. MacMickingJ.D. IFN-γ elicits macrophage autophagy via the p38 MAPK signaling pathway.J. Immunol.2012189281381810.4049/jimmunol.1102041 22675202
    [Google Scholar]
  28. BernsS.A. IsakovaJ.A. PekhterevaP.I. Therapeutic potential of interferon-gamma in tuberculosis.ADMET DMPK2022101637310.5599/admet.1078
    [Google Scholar]
  29. ChinK.L. AnisF.Z. SarmientoM.E. NorazmiM.N. AcostaA. Role of interferons in the development of diagnostics, vaccines, and therapy for tuberculosis.J. Immunol. Res.2017201711010.1155/2017/5212910 28713838
    [Google Scholar]
  30. DesvignesL. WolfA.J. ErnstJ.D. Dynamic roles of type I and type II IFNs in early infection with Mycobacterium tuberculosis.J. Immunol.2012188126205621510.4049/jimmunol.1200255 22566567
    [Google Scholar]
  31. KohG.C.K.W. SchreiberM.F. BautistaR. Host responses to melioidosis and tuberculosis are both dominated by interferon-mediated signaling.PLoS One201381e5496110.1371/journal.pone.0054961 23383015
    [Google Scholar]
  32. LiangG. MalmuthugeN. GuanY. RenY. GriebelP.J. GuanL.L. Altered microRNA expression and pre-mRNA splicing events reveal new mechanisms associated with early stage Mycobacterium avium subspecies paratuberculosis infection.Sci. Rep.2016612496410.1038/srep24964 27102525
    [Google Scholar]
  33. LiuY. WangX. JiangJ. CaoZ. YangB. ChengX. Modulation of T cell cytokine production by miR-144* with elevated expression in patients with pulmonary tuberculosis.Mol. Immunol.2011489-101084109010.1016/j.molimm.2011.02.001 21367459
    [Google Scholar]
  34. KimH.J. KimI.S. LeeS.G. MiR-144-3p is associated with pathological inflammation in patients infected with Mycobacteroides abscessus.Exp. Mol. Med.202153113614910.1038/s12276‑020‑00552‑0 33473145
    [Google Scholar]
  35. VakhrushevaD.V. KrasnoborovaS.Yu. PetruninaE.M. The effectiveness of interferon gamma inclusion in the tuberculosis chemotherapy: Experimental study.Immunologiya202344220921810.33029/0206‑4952‑2023‑44‑2‑209‑218
    [Google Scholar]
  36. AhmedM. MackenzieJ. TezeraL. Mycobacterium tuberculosis senses host Interferon-γ via the membrane protein MmpL10.Commun. Biol.202251131710.1038/s42003‑022‑04265‑0 36456824
    [Google Scholar]
  37. GaoX.F. YangZ.W. LiJ. Adjunctive therapy with interferon-gamma for the treatment of pulmonary tuberculosis: A systematic review.Int. J. Infect. Dis.2011159e594e60010.1016/j.ijid.2011.05.002 21715206
    [Google Scholar]
  38. DawsonR. CondosR. TseD. Immunomodulation with recombinant interferon-gamma1b in pulmonary tuberculosis.PLoS One200949e698410.1371/journal.pone.0006984 19753300
    [Google Scholar]
  39. ShevchukD.V. KuznetsovO.E. Laboratory research methods in differential diagnosis of tuberculosis Pre-analytical stage of laboratory research (methodological recommendations for senior students and physicians).Grodno2006
    [Google Scholar]
  40. SvirshchevskaiaE.V. MitrofanovB.C. ShenderovaR.I. ChuzhovaN.M. Immunity in tuberculosis and aspergillosis.Probl Med Mycol200571313
    [Google Scholar]
  41. KhryaninA.A. ReshetinikovO.V. Interferon-gamma: Treatment horizons.Antibiot. Khimioter.2016613540 29874451
    [Google Scholar]
  42. YeZ. HuY. TGF β1: Gentlemanly orchestrator in idiopathic pulmonary fibrosis.(Review). Int. J. Mol. Med.202148113210.3892/ijmm.2021.4965 34013369
    [Google Scholar]
  43. InuiN. SakaiS. KitagawaM. Molecular pathogenesis of pulmonary fibrosis, with focus on pathways related to TGF-β and the ubiquitin-proteasome pathway.Int. J. Mol. Sci.20212211610710.3390/ijms22116107 34198949
    [Google Scholar]
  44. KangH. Role of micrornas in TGF-β signaling pathway-mediated pulmonary fibrosis.Int. J. Mol. Sci.20171812252710.3390/ijms18122527 29186838
    [Google Scholar]
  45. SaitoA. HorieM. NagaseT. TGF-β signaling in lung health and disease.Int. J. Mol. Sci.2018198246010.3390/ijms19082460 30127261
    [Google Scholar]
  46. ChandaD. OtoupalovaE. SmithS.R. VolckaertT. De LangheS.P. ThannickalV.J. Developmental pathways in the pathogenesis of lung fibrosis.Mol. Aspects Med.201965566910.1016/j.mam.2018.08.004 30130563
    [Google Scholar]
  47. MilyA. RekhaR.S. KamalS.M. ArifuzzamanA.S. RahimZ. KhanL. Significant effects of oral phenylbutyrate and vitamin D3 adjunctive therapy in pulmonary tuberculosis: A randomized controlled trial.PLoS One2015109e0138340
    [Google Scholar]
  48. ReichmuthM.L. HomkeR. ZurcherK. SanderP. AvihingsanonA. CollantesJ. Natural polymorphisms in mycobacterium tuberculosis conferring resistance to delamanid in drug-naive patients.Antimicrob. Agents Chemother.20206411e00513e00520
    [Google Scholar]
  49. RestrepoBI Metformin: Candidate host-directed therapy for tuberculosis in diabetes and non-diabetes patients. Tuberculosis (Edinb)2016101SS6972
    [Google Scholar]
  50. WHO consolidated guidelines on drug-resistant tuberculosis treatment. 2019. Available from:https://iris.who.int/bitstream/handle/10665/311389/9789241550529-eng.pdf
  51. WHO Updates Definition of XDR-TB. 2021. Available from: https://www.who.int/publications/i/item/meeting-report-of-the-who-expert-consultation-on-the-definitionof-extensively-drug-resistant-tuberculosis https://www.who.int/news/item/27-01-2021-who-announces-updated-definitions-of-extensively-drug-resistant-tuberculosis [Accessed 12 dec 2023]
  52. PaikS. KimJ.K. ChungC. JoE.K. Autophagy: A new strategy for host-directed therapy of tuberculosis.Virulence2019101448459
    [Google Scholar]
  53. MartinotA.J. Microbial offense vs host defense: Who controls the TB granuloma?Vet. Pathol.2018551142610.1177/0300985817705177 28749750
    [Google Scholar]
  54. Milanés-VirellesM.T. García-GarcíaI. Santos-HerreraY. Adjuvant interferon gamma in patients with pulmonary atypical Mycobacteriosis: A randomized, double-blind, placebo-controlled study.BMC Infect. Dis.2008811710.1186/1471‑2334‑8‑17 18267006
    [Google Scholar]
  55. RussellS.L. LamprechtD.A. MandizvoT. JonesT.T. NaidooV. AddicottK.W. Compromised metabolic reprogramming is an early indicator of CD8+ T cell dysfunction during chronic mycobacterium tuberculosis infection.Cell Rep.2019291135643579.e5
    [Google Scholar]
  56. ParkH.E. LeeW. ShinM.K. ShinS.J. Understanding the reciprocal interplay between antibiotics and host immune system: How can we improve the anti-mycobacterial activity of current drugs to better control tuberculosis?Front. Immunol.202112703060
    [Google Scholar]
  57. SchoenbornJ.R. WilsonC.B. Regulation of interferon-gamma during innate and adaptive immune responses.Adv. Immunol.20079641101
    [Google Scholar]
  58. SekyereJ.O. ManingiN. FourieP.B. Mycobacterium tuberculosis, antimicrobials, immunity, and lung-gut microbiota crosstalk: Current updates and emerging advances.Ann. N. Y. Acad. Sci.2020146712147
    [Google Scholar]
  59. MancaC. KooM.S. PeixotoB. FallowsD. KaplanG. SubbianS. Host targeted activity of pyrazinamide in Mycobacterium tuberculosis infection.PLoS One201388e7408210.1371/journal.pone.0074082 24015316
    [Google Scholar]
  60. ShanmuganathanG. OrujyanD. NarinyanW. Role of interferons in mycobacterium tuberculosis infection.Clin. Pract.2022125788796
    [Google Scholar]
  61. PearlJ.E. SaundersB. EhlersS. OrmeI.M. CooperA.M. Inflammation and lymphocyte activation during mycobacterial infection in the interferon-gamma-deficient mouse.Cell. Immunol.200121114350
    [Google Scholar]
  62. MacMickingJ.D. Interferon-inducible effector mechanisms in cell-autonomous immunity.Nat. Rev. Immunol.201212536738210.1038/nri3210 22531325
    [Google Scholar]
  63. CoxD.J. ColemanA.M. GoganK.M. Inhibiting histone deacetylases in human macrophages promotes glycolysis, IL-1β, and T helper cell responses to Mycobacterium tuberculosis.Front. Immunol.20201111160910.3389/fimmu.2020.01609 32793237
    [Google Scholar]
  64. EtokebeG.E. Bulat-KardumL. JohansenM.S. Interferon-γ gene (T874A and G2109A) polymorphisms are associated with microscopy-positive tuberculosis.Scand. J. Immunol.200663213614110.1111/j.1365‑3083.2005.01716.x 16476013
    [Google Scholar]
  65. DrainP.K. BajemaK.L. DowdyD. Incipient and subclinical tuberculosis: A clinical review of early stages and progression of infection.Clin. Microbiol. Rev.2018314e00021e1810.1128/CMR.00021‑18 30021818
    [Google Scholar]
  66. FlynnJ.L. ChanJ. TrieboldK.J. DaltonD.K. StewartT.A. BloomB.R. An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection.J. Exp. Med.199317862249225410.1084/jem.178.6.2249 7504064
    [Google Scholar]
  67. DarnellJ.E.Jr KerrM. StarkG.R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins.Science199426451641415142110.1126/science.8197455 8197455
    [Google Scholar]
  68. HawnT.R. MathesonA.I. MaleyS.N. VandalO. Host-directed therapeutics for tuberculosis: Can we harness the host?Microbiol. Mol. Biol. Rev.201377460862710.1128/MMBR.00032‑13 24296574
    [Google Scholar]
  69. EhrtS. SchnappingerD. BekiranovS. Reprogramming of the macrophage transcriptome in response to interferon-gamma and Mycobacterium tuberculosis: Signaling roles of nitric oxide synthase-2 and phagocyte oxidase.J. Exp. Med.200119481123114010.1084/jem.194.8.1123 11602641
    [Google Scholar]
  70. GenestetC. Bernard-BarretF. HodilleE. Antituberculous drugs modulate bacterial phagolysosome avoidance and autophagy in Mycobacterium tuberculosis-infected macrophage.Tuberculosis (Edinb.)2018111677010.1016/j.tube.2018.05.014 30029917
    [Google Scholar]
  71. FortesA. PereiraK. AntasP.R.Z. Detection of in vitro interferon-γ and serum tumour necrosis factor-α in multidrug-resistant tuberculosis patients.Clin. Exp. Immunol.2005141354154810.1111/j.1365‑2249.2005.02872.x 16045745
    [Google Scholar]
  72. CasanovaJ.L. AbelL. Genetic dissection of immunity to mycobacteria: The human model.Annu. Rev. Immunol.200220158162010.1146/annurev.immunol.20.081501.125851 11861613
    [Google Scholar]
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