Abstract
Influenza-like illness (ILI) remains a major cause of severe mortality and morbidity in the elderly. Aging is associated with a decreased ability to sense pathogens and mount effective innate and adaptive immune responses, thus mandating the development of protective nutraceuticals. Biobran/MGN-3, an arabinoxylan from rice bran, has potent anti-aging and immunomodulatory effects, suggesting that it may be effective against ILI. The objective of the current study was to investigate the effect of Biobran/MGN-3 on ILI incidence, natural killer (NK) cell activity, and the expressions of RIG-1 (retinoic acid-inducible gene 1), MDA5 (melanoma differentiation-associated protein 5), and their downstream signaling genes ISG-15 (interferon-stimulated genes 15) and MX1 (myxovirus (influenza) resistance 1, interferon-inducible). A double-blind, placebo-controlled clinical trial included eighty healthy older adults over 55 years old, 40 males and 40 females, who received either a placebo or Biobran/MGN-3 (500 mg/day) for 3 months during known ILI seasonality (peak incidence) in Egypt. The incidence of ILI was confirmed clinically according to the WHO case definition criteria. Hematological, hepatic, and renal parameters were assessed in all subjects, while the activity of NK and NKT (natural killer T) cells was assessed in six randomly chosen subjects in each group by the degranulation assay. The effect of Biobran/MGN-3 on RIG-1 and MDA5, as well as downstream ISG15 and MX1, was assessed in BEAS-2B pulmonary epithelial cells using flow cytometry. The incidence rate and incidence density of ILI in the Biobran/MGN-3 group were 5.0% and 0.57 cases per 1000 person-days, respectively, compared to 22.5% and 2.95 cases per 1000 person-days in the placebo group. Furthermore, Biobran/MGN-3 ingestion significantly enhanced NK activity compared to the basal levels and to the placebo group. In addition, Biobran/MGN-3 significantly upregulated the expression levels of RIG-1, MDA5, ISG15, and MX1 in the human pulmonary epithelial BEAS-2B cell lines. No side effects were observed. Taken together, Biobran/MGN-3 supplementation enhanced the innate immune response of elderly subjects by upregulating the NK activity associated with reduction of ILI incidence. It also upregulated the intracellular RIG-1, MDA5, ISG15, and MX1 expression in pulmonary epithelial tissue cultures. Biobran/MGN-3 could be a novel agent with prophylactic effects against a wide spectrum of respiratory viral infections that warrants further investigation.
Highlights
Influenza-like illness (ILI) is a viral infection with characteristic annual seasonality that leads to around 3–5 million severe illnesses and an estimated 500,000 annual deaths around the world [1,2]
This indicates that Biobran/MGN-3 did not adversely affect any of the hematological, liver, or renal functions
This finding is consistent with previous studies demonstrating that Biobran/MGN-3 is safe without any adverse effects [46,49,55,56]
Summary
Influenza-like illness (ILI) is a viral infection with characteristic annual seasonality that leads to around 3–5 million severe illnesses and an estimated 500,000 annual deaths around the world [1,2]. The World Health Organization (WHO) has recently revised the definition of ILI to be “acute respiratory illness with a measured temperature of ≥38 ◦ C and cough, with onset within the past 10 days” [3]. To enhance the sensitivity of influenza surveillance systems to capture influenza, ILI has been recommended by the WHO to be used as a surrogate for influenza infection [4]. In most surveillance systems around the world, a wide array of viruses has been isolated from ILI cases, including the respiratory syncytial virus, metapneumovirus, corona viruses, adenoviruses, rhinoviruses, and others [4,5,6,7].
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