Treatment of multidrug-resistant pulmonary tuberculosis with interferon-γ via aerosol

Condos, Rany; Rom, William N.; Schluger, Neil W.

doi:10.1016/s0140-6736(96)12273-x

Cited by 296 publications

(188 citation statements)

References 15 publications

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“…Disease Targets IFN-α Hepatitis B and C [5] IFN-β Multiple sclerosis [5] IFN-γ Chronic granulomatous disease [38], Crohn's disease [65], Multidrug resistant tuberculosis [42] TNF-α Rheumatoid arthritis [30,31], Sepsis [32], Refractory asthma [33], Psoriasis [2] G-CSF Idiopathic neutropenia, Congenital neutropenia, Febrile neutropenia, Leukemic neutropenia, Aplastic neutropenia [37], Bone marrow suppression [5] GM-CSF Bone marrow suppression, Crohn's disease [5] IL-2 Metastatic melanoma, Renal cell carcinoma [46] IL-4 Asthma [43] IL-5 Asthma [44] IL-6 Rheumatic diseases [34] IL-10 Crohn's disease, Ulcerative colitis [2], Psoriasis, Rheumatoid arthritis [5] IL-11 Crohn's disease, Ulcerative colitis, Psoriasis, Rheumatoid arthritis [2] IL-13 Asthma [2,45] Erythropoietin Anaemia, Bone marrow failure [5] HER2-Specific Monoclonal Antibody Adenocarcinoma of stomach, Breast cancer [35,36] …”

Section: Cytokinesmentioning

confidence: 99%

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Cytokines and their Role in Health and Disease: A Brief Overview

Gulati¹,

Guhathakurta²,

Joshi³

et al. 2016

MOJI

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Cytokines are small, non-structural proteins with low molecular weights which have a complex regulatory influence on inflammation and immunity. It has long been considered that development of immune and inflammatory response involves hematopoietic cells, lymphoid cell, and various pro-inflammatory and anti-inflammatory cells, and cytokines mediate the complex interactions of these cells. Cytokines are the intercellular messengers in the immune system where they integrate function of several cell types in various body compartments into a coherent immune response. They have evolved over the years and now include the interferons, the interleukins, the chemokine family, mesenchymal growth factors, the tumor necrosis factor family and adipokines. Earlier known as `soluble factors`, cytokines are produced by and elicit a response from every cell, with the lone exception of the red blood cell. In response to various stimulus cytokines are secreted from various cells including white blood cells. Pleiotropism is the hallmark of a cytokine and there are failures and successes of cytokines and related agents as therapeutic agents. In the membrane of target cells they have specific receptors for their signal transduction and regulatory functions. Beyond the innate and adaptive immunity, cytokines has a major role in many diverse functions including immune cell differentiation, inflammation, angiogenesis, tumorigenesis, neurobiology, viral pathogenesis etc. In addition to inflammation, immunity and infections, cytokines have now expanded their domain to atherosclerosis and cancer. Thus, cytokines may be useful biomarkers for health and disease and act as diagnostic, prognostic and therapeutic agents. This review will highlight the impact of cytokines in various physiological actions, pathophysiological states, therapeutics and the complex interactions between brain and immune cells. knowledge has highlighted the complexity and biphasic nature of cytokines -and the same molecule may have beneficial as well as detrimental effects. For example, interferon-γ (IFNγ), which is essential for defense against several intracellular microorganism such as Mycobacterium tuberculosis, is also a major cytokine in the pathogenesis of several autoimmune diseases. IL-2 is needed for the generation of cytotoxic T-cells (CTL) and forms the basis for several vaccines but the same cytokine drives graft versus host disease and limits the success of bone marrow transplantation [5]. Keywords: Cytokine ReceptorsThe cytokines exert various biological effects through receptors present on the membranes of responsive target cells. These receptors have an extracellular domain, a cytoplasmic domain and a single membrane spanning domain. There is the presence of conserved amino acid sequence motifs on the extracellular domain and these motifs include four conserved cysteine residues. There is also the presence of two polypeptide chains. One is the cytokine specific α subunit and other is a signal transducing β subunit.The nature of the target cell ...

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Section: Cytokinesmentioning

confidence: 99%

“…It also activates alveolar macrophages and plays an effective role in host immunity against M. tuberculosis. IFN-γ as an aerosol form has been used in multidrug-resistant tuberculosis patients [42]. Antibodies against cytokines like IL-4, IL-5, IL-13 are used for the treatment of asthma.…”

mentioning

confidence: 99%

Cytokines and their Role in Health and Disease: A Brief Overview

Gulati¹,

Guhathakurta²,

Joshi³

et al. 2016

MOJI

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“…Moreover, aerosol administration of IFN-␥ has reported efficacy in patients with multidrug-resistant TB (33). T cell activation is influenced by Fc␥RIIB regulation of APCs, including the capacity of which T lymphocytes make IFN-␥ (26,27).…”

Section: Riib ϫ/ϫ Mice Have Increased Ifn-␥ Production and Ifn-␥-prodmentioning

confidence: 99%

Fcγ Receptors Regulate Immune Activation and Susceptibility during Mycobacterium tuberculosis Infection

Maglione

Casadevall

et al. 2008

The Journal of Immunology

137

152

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The critical role of cellular immunity during tuberculosis (TB) has been extensively studied, but the impact of Abs upon this infection remains poorly defined. Previously, we demonstrated that B cells are required for optimal protection in Mycobacterium tuberculosis-infected mice. FcγR modulate immunity by engaging Igs produced by B cells. We report that C57BL/6 mice deficient in inhibitory FcγRIIB (RIIB−/−) manifested enhanced mycobacterial containment and diminished immunopathology compared with wild-type controls. These findings corresponded with enhanced pulmonary Th1 responses, evidenced by increased IFN-γ-producing CD4+ T cells, and elevated expression of MHC class II and costimulatory molecules B7-1 and B7-2 in the lungs. Upon M. tuberculosis infection and immune complex engagement, RIIB−/− macrophages produced more of the p40 component of the Th1-promoting cytokine IL-12. These data strongly suggest that FcγRIIB engagement can dampen the TB Th1 response by attenuating IL-12p40 production or activation of APCs. Conversely, C57BL/6 mice lacking the γ-chain shared by activating FcγR had enhanced susceptibility and exacerbated immunopathology upon M. tuberculosis challenge, associated with increased production of the immunosuppressive cytokine IL-10. Thus, engagement of distinct FcγR can divergently affect cytokine production and susceptibility during M. tuberculosis infection.

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“…This was accomplished via a constant source. In a second simulation, single injections of I g treatment (at 100 pg of each) were given 3 times a week over a 33 day period starting on Day 7 (57). Future work will address the particulars mentioned above regarding IFN-␥ drug properties and employ control algorithms to determine optimal dosing regimens.…”

Section: Ifn-␥ Protocolsmentioning

confidence: 99%

Modeling the immune rheostat of macrophages in the lung in response to infection

Day¹,

Friedman²,

Schlesinger

2009

Proc. Natl. Acad. Sci. U.S.A.

126

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In the lung, alternatively activated macrophages (AAM) form the first line of defense against microbial infection. Due to the highly regulated nature of AAM, the lung can be considered as an immunosuppressive organ for respiratory pathogens. However, as infection progresses in the lung, another population of macrophages, known as classically activated macrophages (CAM) enters; these cells are typically activated by IFN-␥. CAM are far more effective than AAM in clearing the microbial load, producing proinflammatory cytokines and antimicrobial defense mechanisms necessary to mount an adequate immune response. Here, we are concerned with determining the first time when the population of CAM becomes more dominant than the population of AAM. This proposed ''switching time'' is explored in the context of Mycobacterium tuberculosis (MTb) infection. We have developed a mathematical model that describes the interactions among cells, bacteria, and cytokines involved in the activation of both AAM and CAM. The model, based on a system of differential equations, represents a useful tool to analyze strategies for reducing the switching time, and to generate hypotheses for experimental testing.alternatively activated macrophages ͉ lung innate immunity ͉ mycobacteria tuberculosis

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Treatment of multidrug-resistant pulmonary tuberculosis with interferon-γ via aerosol

Cited by 296 publications

References 15 publications

Cytokines and their Role in Health and Disease: A Brief Overview

Cytokines and their Role in Health and Disease: A Brief Overview

Fcγ Receptors Regulate Immune Activation and Susceptibility during Mycobacterium tuberculosis Infection

Modeling the immune rheostat of macrophages in the lung in response to infection

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