Immunomodulatory effect of pleuran (β-glucan from Pleurotus ostreatus) in children with recurrent respiratory tract infections
Highlights
► We confirmed the efficacy of pleuran on the prevention of respiratory infections. ► We revealed complex immunomodulatory activity of pleuran in vivo. ► We observed that the immunoglobulin isotypes increase due to treatment with pleuran. ► Pleuran supports the natural maturation of immune system in children. ► We add new valuable data to the immunomodulatory potential of β-glucans in human.
Introduction
Physicians are challenged by the difficulty in diagnosing and treating recurrent respiratory tract infections (RRTIs). According to the epidemiological studies, approximately 6% of children younger than 6 years of age suffer from RRTIs. In developed countries, up to 25% of children less than 1 year of age and 18% of children between the ages of 1 to 4 years experience RRTIs [1]. These figures have increased the awareness of RRTIs among the medical community.
The definitions of RRTIs are too arbitrary, too generic, or too restrictive. However, at least one of the following criteria has to be present to diagnose an RRTI: ≥ 6 respiratory infections per year; ≥ 1 respiratory infection per month involving the upper airways from September to April; or ≥ 3 respiratory infections per year involving the lower airways [2]. Thus, physicians must determine whether the high morbidity caused by respiratory infections in normal children is related to the physiological immaturity of the immune system. Physicians must also assess whether increased exposure to environmental risk factors alters other underlying pathological conditions (immunological or not), thereby predisposing these children to respiratory infections [3], [4]. The majority of children with RRTIs do not have recognised immunodeficiencies, but some children may have low levels of certain immunological parameters, such as reduced levels of immunoglobulin isotypes. However, a number of the observed immunological alterations are of questionable significance and may not be related to the increased susceptibility to respiratory infections [5].
The management of children with RRTIs consists of excluding other pathological conditions that result in respiratory infections by administering the appropriate treatment. Children diagnosed with classical RRTIs are usually treated with immunomodulation. Many available preparations have a potential or confirmed immunomodulatory effects to prevent and treat respiratory infections in children. However, the therapeutic efficacy of only a few of these preparations has been evaluated in controlled clinical trials.
In our previous open label study, we investigated the effect of Imunoglukan P4H® (pleuran, insoluble β-glucan isolated from Pleurotus ostreatus combined with vitamin C) in a group of children suffering from RRTIs [6]. β-Glucans possess immunomodulatory activity in both non-specific and specific arms of immune response [7]. The use of pleuran resulted in increased NK-cell number [8], [9], stimulated phagocytic activity and enhanced post-vaccination antibody production [10]. Vitamin C, which is also contained in the syrup, has confirmed several immunomodulatory effects, either on the stimulation of lymphocytes proliferation [11] and phagocytic activity [12], on the production of different cytokines (e.g. interferon gamma) [13], [14] or through the stimulation of cellular immunity [15]. The combination of pleuran and vitamin C therefore could provide beneficial simultaneous immunomodulatory activity, resulting in a synergistic clinical effect. Our previously published open clinical trial confirmed the effect of Imunoglukan P4H® on the decline of respiratory morbidity in children. There were no side effects observed during this trial [6]. Based on these promising results, we have designed a randomised, multicentre, double blind, placebo-controlled study, in which we investigated the preventive clinical effect and immunomodulatory activity of Imunoglukan P4H® (pleuran, insoluble β-glucan isolated from P. ostreatus combined with vitamin C) in the group of children suffering from RRTIs. As we have observed a vulnerable population of children, mainly for ethical reasons, we have decided to use an active placebo in the form of vitamin C.
Section snippets
Materials and methods
This study enrolled children (n = 175) between the ages of 2 and 10 years with a history of RRTIs. Children between the ages of 2 and 5 years and between the ages of 6 and 10 years were diagnosed with > 5 and > 3 respiratory infections each year, respectively. Patients with a history of serious internal disorders were not able to participate in the study and were excluded. Furthermore, patients who were treated with other immunomodulators or with antibiotics 14 days prior to enrolment were also
Results
The demographic characteristics of the studied population are presented in Table 1. The two groups of the studied children did not differ in gender, age, mean weight, or number of upper respiratory tract infections (URTIs) in the previous 12 months or proportion of atopic children (Table 1). The number of children younger than 5 years of age was similar in both groups, with 52 (55.3%) and 47 (58.0%) in the active and placebo treatment groups, respectively (p = 0.761).
Active treatment resulted in a
Discussion
In our double blind, placebo-controlled clinical trial, we investigated the clinical efficacy and immunomodulatory effect of a natural immunomodulator, Imunoglukan P4H®. Our results showed a significant decline in respiratory morbidity, including a decrease in the number of RRTIs in the active group. Imunoglukan P4H® treatment also resulted in complex immunomodulatory activity on innate and adaptive immunity. The increase in all three immunoglobulin isotypes demonstrated that Imunoglukan P4H®
Acknowledgement
We would like to thank Geoffry Nuttall, MRPharmS, for his comments on this manuscript. The study was supported by Pleuran Ltd.
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