Oral cytokine administration

Rollwagen, Florence M.; Baqar, Shahida

doi:10.1016/s0167-5699(96)30065-0

Cited by 77 publications

(34 citation statements)

References 9 publications

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“…Regarding the attempt to develop very low-dose cytokine administration, this choice is in accordance with data of literature, suggesting that low doses of cytokines are adequate in many different models [22]; the low-dose effects in these models strongly suggest the induction of a secondary mode of action, perhaps the induction of cytokine secretion in cells other than the ones directly stimulated by the administered cytokines. For example, in vivo experiments of low-dose interferon-α treatment have been described in many animal species [11]; such a treatment was shown to induce dramatic clinical amelioration in models of both infectious and chronic inflammatory diseases [42].…”

Section: Discussionsupporting

confidence: 73%

“…Systemic administration is not an efficient way to deliver cytokines to specific inductive sites, while administration of cytokines via the oral route offers an exciting alternative to systemic application, for ease of dispensation. Increasing evidence suggests that oral administration of certain cytokines is not only safe and effective, but also avoids the deleterious consequences of systemic administration, retaining sufficient biological activity to effect immunomodulatory functions beyond the local mucosa [22]. [5], IFN-γ is thought to be critically involved in down-modulating Th2 cell-driven asthma.…”

Section: Discussionmentioning

confidence: 99%

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Low dose oral administration of cytokines for treatment of allergic asthma

Gariboldi

Palazzo

Zanobbio

et al. 2009

Pulmonary Pharmacology & Therapeutics

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Many inflammatory diseases are characterized by an imbalance among lymphocyte populations, in particular Th1, Th2 and the recently described Th17 cells. The Th1/Th2 imbalance is linked to many factors, but certainly the role of cytokines is essential.In Th2 diseases IL-4 expression is predominant, while Th1 pathologies are characterized by high expression of IFN-γ and IL-12. Though today the therapeutical proposal for many inflammatory diseases aims to re-establish normal levels of Th1/Th2 cytokines, the pharmacological use of cytokines, which are very active molecules, is limited by the possible collateral effects. Therefore, our study aims to determine, in a murine model of allergic asthma, the possible therapeutic activity of low dose cytokines solutions, mechanically activated. We found that oral administration of low doses IL-12 plus IFN-γ is able to solve the bronchial hyperresponsiveness condition of mice, establishing normal cytokine levels. The anti-asthma activity was confirmed by histological analysis of lungs and bronchoalveolar lavage fluid cell count. Serum ovalbumin-specific IgE was also significantly inhibited by treatment with low-dose activated cytokines solution. These findings may suggest a novel approach to diseases which involve a Th1/Th2 imbalance.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Low dose oral administration of cytokines for treatment of allergic asthma

Gariboldi

Palazzo

Zanobbio

et al. 2009

Pulmonary Pharmacology & Therapeutics

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“…These results also suggest that combination therapy of other autoantigens along with one or more regulatory Th2 cytokines given orally to enhance protection may represent an important new strategy in the prevention of autoimmune diseases through a form of forced manipulation of antigen-specific Th1:Th2 T cell populations (28). In contrast to systemic delivery of IL-4, which leads to numerous side effects in humans (29), oral IL-4 seemed to be well tolerated in mice. The efficacy of oral human IL-4 to induce protection in patients without systemic adverse effects remains to be tested, but these data would support this approach.…”

Section: Discussionmentioning

confidence: 93%

“…The oral administration of cytokines for therapies has been suggested (29). Type I IFN has been shown to resist digestive enzymes present in the gut (29).…”

Section: Discussionmentioning

confidence: 99%

Induction of oral tolerance to prevent diabetes with transgenic plants requires glutamic acid decarboxylase (GAD) and IL-4

Huang

Yin

et al. 2004

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

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Induction of specific immunological unresponsiveness by feeding protein antigens is termed oral tolerance and may be a potential therapy for autoimmune diseases. Whereas oral tolerance therapy may be both simple and effective, the requirement for large amounts of protein will limit clinical testing of autoantigens, which are difficult to produce. We have previously demonstrated transgenic plant production and direct oral delivery of a ␤ cell autoantigen murine GAD67 to prevent autoimmune diabetes in nonobese diabetic mice. Mucosal adjuvants such as cholera toxin B subunit may lower the level of autoantigen required, but the development of neutralizing mucosal antibody responses may limit usefulness in enhancing long-term oral tolerance. IL-4, being an endogenous protein, would avoid this result and possibly enhance oral tolerance but has not been tested as a mucosal adjuvant. In this study, human GAD65 (hGAD65), as well as murine IL-4, was expressed in transgenic plants for feeding trials. Both IL-4 and hGAD65 plant tissue were required to protect nonobese diabetic mice from diabetes, and no benefit was found if either was used alone. Combined therapy enhanced levels of IgG1 anti-GAD antibodies, increased splenocyte IL-4͞IFN-␥ cytokine responses, and produced protective regulatory T cells. These results demonstrate that orally administered plant IL-4 remains biologically active and is synergistic when given with hGAD65 in inducing robust oral immune tolerance. Using transgenic plants expressing IL-4 and GAD65 may be a novel clinical approach to the prevention of human type 1 diabetes by oral tolerance.

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“…Oral administration of cytokines has been recognized to be safe and effective for modulating immune responses in the treatment of inflammatory, autoimmune, and allergic disorders (Rollwagen and Baqar 1996). In an experimental allergic encephalomyelitis model, the effect of orally fed IL-10 was previously examined using myelin basic protein (MBP) as a model antigen.…”

mentioning

confidence: 99%

Efficacy of transgenic rice containing human interleukin-10 in experimental mouse models of colitis and pollen allergy

Takagi

Watanabe

Hiroi

et al. 2015

Plant Biotechnology

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Recombinant human interleukin-10 (hIL-10) is highly expressed in transgenic rice endosperm and forms active homodimers in the ER-derived hIL-10 body. In this study, we examined the preclinical efficacy of transgenic rice accumulating hIL-10 (hIL-10 rice) in in vivo experimental mouse models of colitis and pollen allergy. In the group of mice orally fed hIL-10 rice, the development of Japanese cedar pollen allergen-specific IgE and splenic T cell responses were significantly inhibited. In addition, oral feeding of hIL-10 rice showed therapeutic as well as prophylactic efficacy against experimental colitis developed in IL-10-deficient mice. These results indicate the clinical potentiality of hIL-10 rice for the control of inflammatory and allergic disorders through efficient delivery of hIL-10 to the gut-associated lymphoid tissue.

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Oral cytokine administration

Cited by 77 publications

References 9 publications

Low dose oral administration of cytokines for treatment of allergic asthma

Low dose oral administration of cytokines for treatment of allergic asthma

Induction of oral tolerance to prevent diabetes with transgenic plants requires glutamic acid decarboxylase (GAD) and IL-4

Efficacy of transgenic rice containing human interleukin-10 in experimental mouse models of colitis and pollen allergy

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