Ingested IFN-α

Brod, Staley A.; Lindsey, J. W.; Vriesendorp, F. S.; Ahn, Chul Woo; Henninger, Evelyn; Narayana, Ponnada A.; Wolinsky, Jerry S.

doi:10.1212/wnl.57.5.845

Cited by 28 publications

(13 citation statements)

References 46 publications

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“…Most importantly, we have also demonstrated that IFN-, in contrast to IFN-␣ or IFN-␤, does not promote secretion of IFN-␥, an attractive feature of this type I IFN, which could also contribute to the different clinical observations made in these two studies. This key pharmacodynamic difference between IFN-and IFN-␣ should be considered in view of the results from a recent pilot MS trial using oral IFN-␣ that suggested that oral IFN-␣ may not be effective in treatment of relapsing-remitting MS (23). In addition, patients in that trial received either 10,000 or 30,000 U of IFN-␣.…”

Section: Resultsmentioning

confidence: 99%

Cutting Edge: Oral Type I IFN-τ Promotes a Th2 Bias and Enhances Suppression of Autoimmune Encephalomyelitis by Oral Glatiramer Acetate

Soos

Stüve

Youssef

et al. 2002

The Journal of Immunology

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IFN-τ, a novel type I IFN that possesses immunomodulatory properties, lacks toxicity normally associated with other type I IFNs. We examined the effects of oral IFN-τ alone and in combination with oral glatiramer acetate in experimental allergic encephalomyelitis (EAE). By comparison of oral administration of IFN-α, -β, and -τ to myelin basic protein-specific TCR-transgenic mice, we demonstrate these type I IFNs promote secretion of the Th2 cytokine IL-10 with similar efficiency. Whereas IFN-α and -β induced IFN-γ secretion, a Th1 cytokine, IFN-τ did not. Oral IFN-τ alone suppressed EAE. When suboptimal doses were administered orally in combination to wild-type mice, IFN-τ and glatiramer acetate had a synergistic beneficial effect in suppression of EAE. This combination was associated with TGF-β secretion and enhanced IL-10 production. Thus, IFN-τ is a potential candidate for use as a single agent or in combination therapy for multiple sclerosis.

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Section: Resultsmentioning

confidence: 99%

Cutting Edge: Oral Type I IFN-τ Promotes a Th2 Bias and Enhances Suppression of Autoimmune Encephalomyelitis by Oral Glatiramer Acetate

Soos

Stüve

Youssef

et al. 2002

The Journal of Immunology

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“…Entry criteria included newly diagnosed type 1 diabetes mellitus (within 1 month of diagnosis) (n 5 10) (ages [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. Pediatric and adult endocrinologists diagnosed patients with type 1 diabetes mellitus from the inpatient and outpatient registries of the University of Texas Houston Medical School according to American Diabetic Association (ADA) criteria (fasting blood sugar [FBS] .125; 2 h postprandial .200).…”

Section: Subjectsmentioning

confidence: 99%

“…(8) Ingested recombinant human IFN-a (rHuIFN-a) was nontoxic and was a BRM in humans in a phase I clinical trial in relapsing-remitting multiple sclerosis (RRMS), a presumed autoimmune disease, (9) and may reduce gadolinium-enhanced cerebral MRI lesions and proinflammatory tetanus toxoid-induced IFN-g and tumor necrosis factor-a (TNF-a) secretion in RRMS. (10) Stimulation tests are important in assessing residual b cell function in type 1 diabetes. (11) Therefore, we investigated whether ingested IFN-a could preserve residual b cell function for up to 1 year in patients treated within 1 month of diagnosis of type 1 diabetes mellitus in an open-label phase I clinical trial.…”

Section: Introductionmentioning

confidence: 99%

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Ingested IFN-αPreserves ResidualβCell Function in Type 1 Diabetes

Brod¹,

Atkinson

Lavis³

et al. 2001

Journal of Interferon & Cytokine Research

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Type 1 diabetes mellitus is a chronic disorder that presumably results from an autoimmune destruction of the insulin-producing pancreatic beta cells. The therapeutic potential of interventions aimed at preventing type 1 diabetes can be assessed in newly diagnosed patients. Because there is a historical experience of a low incidence of spontaneous remission in type 1 diabetes mellitus, interventions preserving beta cell function have been used to identify positive therapeutic outcomes. We treated 10 newly diagnosed type 1 diabetes patients with 30,000 IU ingested interferon-alpha (IFN-alpha) within 1 month of diagnosis and examined the difference between baseline and Sustacal-induced (Mead Johnson Nutritionals, Evansville, IN) C-peptide responses, respectively, at 0, 3, 6, 9, and 12 months. Eight of the ten patients showed preserved beta cell function, with at least a 30% increase in stimulated C-peptide levels at 0, 3, 6, 9, and 12 months after initiation of treatment. There was no discernible chemical or clinical toxicity associated with ingested IFN-alpha. Our results support the potential of ingested IFN-alpha to preserve residual beta cell function in recent onset type 1 diabetes mellitus and the testing of IFN-alpha in a placebo-controlled trial.

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“…Because we detected changes in immune response and post hoc analysis suggested that the 10,000 IU dose may have an effect, ingested IFN-␣ received additional study in dose-response experiments in MS using biologic response markers (BRM). 21 Therefore, we examined MxA mRNA induction and TNF-␣ mRNA repression ex vivo to determine the optimal dose(s) of ingested IFN-␣ for future clinical trials in MS. We used IFN-␣ specifically because of the results from our animal and human experiments and its acid stability and not IFN-␤ because it has not shown bioactivity by mouth in humans. 22,23 …”

Section: Introductionmentioning

confidence: 99%

Ingested (Oral) IFN-α Represses TNF-α mRNA in Relapsing-Remitting Multiple Sclerosis

Brod

Nguyen

Hood

et al. 2006

Journal of Interferon & Cytokine Research

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In a phase II trial in relapsing-remitting multiple sclerosis (RRMS), patients ingesting 10,000 IU, but not 30,000 IU, interferon-alpha (IFN-alpha) showed fewer gadolinium enhancements at months 5 and 6, along with decreased proinflammatory tumor necrosis factor-alpha (TNF-alpha) protein secretion. Therefore, we examined MxA mRNA induction and TNF-alpha mRNA repression after 100, 300, 1,000, 3,000, and 10,000 IU doses of ingested IFN-alpha in 24 RRMS patients to determine the optimal dose for future clinical trials in MS. Maximal TNF-alpha repression occurs at 100, 1,000, and 3,000 IU. These data provide new optimal doses for additional clinical studies using ingested IFN-alpha in MS.

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Ingested IFN-α

Abstract: This trial showed no benefit based on the primary outcome measure. Because changes were detected in immune response and post hoc analysis suggested that a smaller dose could have an effect, IFN-alpha may deserve further study.

Cited by 28 publications

References 46 publications

Cutting Edge: Oral Type I IFN-τ Promotes a Th2 Bias and Enhances Suppression of Autoimmune Encephalomyelitis by Oral Glatiramer Acetate

Cutting Edge: Oral Type I IFN-τ Promotes a Th2 Bias and Enhances Suppression of Autoimmune Encephalomyelitis by Oral Glatiramer Acetate

Ingested IFN-αPreserves ResidualβCell Function in Type 1 Diabetes

Ingested (Oral) IFN-α Represses TNF-α mRNA in Relapsing-Remitting Multiple Sclerosis

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