Abstract

Multiple reports have claimed that low-dose orally administered interferon (IFN)-α is beneficial in the treatment of many infectious diseases and provides a viable alternative to high-dose intramuscular treatment. However, research is needed on how to express IFN stably in the gut. Bifidobacterium may be a suitable carrier for human gene expression and secretion in the intestinal tract for the treatment of gastrointestinal diseases. We reported previously that Bifidobacterium longum can be used as a novel oral delivery of IFN-α. IFN-transformed B. longum can exert an immunostimulatory role in mice; however the answer to whether this recombinant B. longum can be used to treat virus infection still remains elusive. Here, we investigated the efficacy of IFN-transformed B. longum administered orally on coxsackie virus B3 (CVB3)-induced myocarditis in BALB/c mice. Our data indicated that oral administration of IFN-transformed B. longum for 2 weeks after virus infection reduced significantly the severity of virus-induced myocarditis, markedly down regulated virus titers in the heart, and induced a T helper 1 cell pattern in the spleen and heart compared with controls. Oral administration of the IFN-transformed B. longum, therefore, may play a potential role in the treatment of CVB3-induced myocarditis.

Highlights

  • The oral use of low doses of interferon (IFN)-a has been shown to exhibit beneficial effects in mice or human with acquired immunodeficiency syndrome (AIDS) [1], hepatitis B [2], aphthous stomatitis [3], and measles [4]

  • High Mx1 mRNA transcript levels were detected in the BIFN group compared with the saline and B groups respectively (p < 0.01; Figure 2h), a finding that was suggestive of a possibly high type I IFN concentration in this organ. In this experiment, we proved the efficacy of the BIFNtransformed B. longum cells on the coxsackie virus B3 (CVB3)-induced myocarditis

  • Oral administration of IFN-transformed B. longum cells can reduce significantly the cardiac inflammatory area of CVB3-infected mice by day 14 compared with the B and saline groups respectively, which suggested that BIFN-transformed B. longum cells can improve the severity of disease

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Summary

Introduction

The oral use of low doses of interferon (IFN)-a has been shown to exhibit beneficial effects in mice or human with acquired immunodeficiency syndrome (AIDS) [1], hepatitis B [2], aphthous stomatitis [3], and measles [4]. These studies have indicated that IFN-a/-b given orally provides a viable alternative to the current high-dose treatment intramuscularly [5,6]. Oral administration of IFN-transformed B. longum to mice increased intestinal sIgA and serum IFN-a2b levels, which suggested the potential clinical value of this bacterium as a kind of oral interferon in the treatment of virus infection [13]

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