Interferon γ-1b in chronic granulomatous disease and severe malignant osteopetrosis: a guide to its use in the USA

Lyseng‐Williamson, Katherine A.

doi:10.1007/s40267-015-0222-0

Cited by 5 publications

(3 citation statements)

References 37 publications

(78 reference statements)

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“…Some patients with osteopetrosis variants that are not responsive to HSCT or before transplantation have been given interferon gamma 1b (IFNγ1b) therapy. It has been reported to improve the immune function, enhance bone resorption, and increase bone marrow space [17][18].…”

Section: Discussionmentioning

confidence: 99%

Malignant Infantile Osteopetrosis: A Case Report

Bubshait¹,

Fadaaq²,

Alshmas³

2020

Cureus

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Section: Discussionmentioning

confidence: 99%

Malignant Infantile Osteopetrosis: A Case Report

Bubshait¹,

Fadaaq²,

Alshmas³

2020

Cureus

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“…Both conditions result in patients regularly suffering from life threatening infections. Prophylactic treatment with IFN-γ reduces the frequency and relative risk of severe infections and may delay disease progression [4]. Currently, two recombinant IFN-γ products are available; Actimmune® (Horizon Pharma USA, Inc) and Immukin® (Boehringer Ingelheim, Germany).…”

Section: Introductionmentioning

confidence: 99%

Effective nebulization of interferon-γ using a novel vibrating mesh

et al. 2019

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Background Interferon gamma (IFN-γ) is a clinically relevant immunomodulatory cytokine that has demonstrated significant potential in the treatment and management of respiratory diseases such as tuberculosis and pulmonary fibrosis. As with all large biomolecules, clinical translation is dependent on effective delivery to the disease site and delivery of IFN-γ as an aerosol offers a logical means of drug targeting. Effective localization is often hampered by instability and a lack of safe and efficient delivery systems. The present study sought to determine how effectively IFN-γ can be nebulized using two types of vibrating mesh nebulizer, each with differing mesh architectures, and to investigate the comparative efficiency of delivery of therapeutically active IFN-γ to the lungs. Methods Nebulization of IFN-γ was carried out using two different Aerogen vibrating mesh technologies with differing mesh architectures. These technologies represent both a standard commercially available mesh type (Aerogen Solo®) and a new iteration mesh (Photo-defined aperture plate (PDAP®). Extensive aerosol studies (aerosol output and droplet analysis, non-invasive and invasive aerosol therapy) were conducted in line with regulatory requirements and characterization of the stability and bioactivity of the IFN-γ post-nebulization was confirmed using SDS-PAGE and stimulation of Human C-X-C motif chemokine 10 (CXCL 10) also known as IFN-γ-induced protein 10KDa (IP 10) expression from THP-1 derived macrophages (THP-1 cells). Results Aerosol characterization studies indicated that a significant and reproducible dose of aerosolized IFN-γ can be delivered using both vibrating mesh technologies. Nebulization using both devices resulted in an emitted dose of at least 93% (100% dose minus residual volume) for IFN-γ. Characterization of aerosolized IFN-γ indicated that the PDAP was capable of generating droplets with a significantly lower mass median aerodynamic diameter (MMAD) with values of 2.79 ± 0.29 μm and 4.39 ± 0.25 μm for the PDAP and Solo respectively. The volume median diameters (VMD) of aerosolized IFN-γ corroborated this with VMDs of 2.33 ± 0.02 μm for the PDAP and 4.30 ± 0.02 μm for the Solo. SDS-PAGE gels indicated that IFN-γ remains stable after nebulization by both devices and this was confirmed by bioactivity studies using a THP-1 cell model in which an alveolar macrophage response to IFN-γ was determined. IFN-γ nebulized by the PDAP and Solo devices had no significant effect on the key inflammatory biomarker cytokine IP-10 release from this model in comparison to non-nebulized controls. Here we demonstrate that it is possible to combine IFN-γ with vibrating mesh nebulizer devices and facilitate effective aerosolisation with minimal impact on IFN-γ structure or bioactivity. Conclusions It is possible to nebulize IFN-γ effectively with vibrating mesh nebulizer devices without compromising its stability. The PDAP allows for ge...

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“…Interferon gamma 1b (IFNγ1b) treatment has been tried in patients with osteopetrosis variants unresponsive to HSCT or as a bridging therapy to transplantation. It has been reported to result in improvement in immune function, increased bone resorption and increase in bone marrow space [ 9 – 11 ].…”

Section: Discussionmentioning

confidence: 99%

Osteopetrosis in two siblings: two case reports

et al. 2016

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BackgroundOsteopetrosis is a rare inherited metabolic bone disorder characterized by extensive sclerosis of skeletons, visual and hearing impairment, hepatosplenomegaly and anemia. It has two major clinical forms: the autosomal dominant adult (benign) form is associated with milder symptoms often appearing in later childhood and adulthood whereas the autosomal recessive infantile (malignant) form has severe presentations appearing in very early childhood, if untreated, is typically fatal during infancy or early childhood. A rare autosomal recessive (intermediate) form is present during childhood with some signs and symptoms of malignant osteopetrosis. Diagnosis is mainly based on clinical and typical generalized increase in bone density.Case presentationThe two siblings of Indo-Aryan ethnicity, aged five and 8 years, were admitted with irregular low grade fever and gradually increasing abdominal mass for last 3 years. They also had history of hearing loss. On examination, the patients were found pale with poor nutritional status, short stature, frontal bossing and splenomegaly. We made a clinical diagnosis of hemolytic anemia and investigated accordingly. Peripheral Blood Smear was suggestive of leucoerythroblastic picture in both the siblings. We extended our investigations and radiological survey revealed generalized increase in bone density which was consistent with osteopetrosis.ConclusionOsteopetrosis is a rare disease transmitted by autosomal dominant or recessive inheritance having variable penetrance. We report here milder form of disease in the two siblings having typical clinical features in the form of anemia, hepatosplenomegaly and hearing loss. Diagnosis was confirmed by typical generalized increase in bone density in both the patients.

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Interferon γ-1b in chronic granulomatous disease and severe malignant osteopetrosis: a guide to its use in the USA

Abstract: In the USA, subcutaneous interferon c-1b

Cited by 5 publications

References 37 publications

Malignant Infantile Osteopetrosis: A Case Report

Malignant Infantile Osteopetrosis: A Case Report

Effective nebulization of interferon-γ using a novel vibrating mesh

Osteopetrosis in two siblings: two case reports

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