ATOPIC DERMATITIS
Use of ImmunostimTM in the treatment of Atopic Dermatitis
Aspects of innate and adaptive immunity in atopic dermatitis.
Atopic dermatitis (AD) is one of the most common skin disorders affecting predominantly infants and children (1). The term eczema is often used but AD is more precise. Its prevalence in developing countries is between 15-24% with two third persisting to adulthood.
Patients with AD are highly susceptible to cutaneous bacterial, fungal and viral infections (2). However, bacterial colonisation with Staphylococcus aureus in the most common skin infection with 90% of AD compared with 5% of normal subjects. The severity of the disease is related to the number of bacteria in skin. Eradication of the bacteria is associated with improvement in skin lesion. In patients who are refractory to treatment with anti-inflammatory drugs, persistent infection is associated with high levels of IgE that may contribute to the failure to clear the infection from the skin (3). IgE is known to inhibit the mobilization of circulating neutrophils, phagocytosis and the production of reactive oxygen free radicals to combat infection (4).
The innate immune system of the skin is the first line of defence against invading microbes. In patients with AD, skin biopsies showed a striking absence of neutrophils even after increased S.aureus colonisation and infection of the skin damaged by constant and intense scratching. These patients have defective innate immunity characterised by a defective neutrophil chemotactic activity (inability to recruit circulating neutrophils to clear the bacteria at the site of infection) that is associated with disease severity and the presence of persistent infection (5-7). The failure to recruit neutrophils which are critical to the first line of defence and the initiation of an appropriate protective adaptive immune response exposes the patients to a wide range of skin infections. The damage to the skin facilitating invasion of microbes normally mobilizes the innate immunity through the production of a variety of signal molecules in the skin to mount an anti-microbial defence and to recruit neutrophils but in patients with AD this mechanism of host defence is defective.
Another failure of AD patients to clear the infection is the activation of an adaptive immunity in the skin of disease promoting Th2 rather than Th1 cells by S. aureus (8) resulting in the chronicity of inflammation that characterises AD. Reduction in cutaneous S. aureus bacteria and lesion by treatment of AD patients with immunosuppressive agents such as corticosteroid is probably the result of the suppression of Th2 response. Thus a strategy to promote a strong Th1 response by suppressing a Th2 response in the skin is desirable to effectively clear cutaneous infections.
How Immunostim can do the job
Immunostim is comprised of two clinically-proven effective and safe products, lactoferrin and polysaccharide-K, which target the respective innate and adaptive immunity. Innate immunity is endowed with recognition cell surface receptors and anti-microbial proteins that provide an immediate response to danger posed by invading pathogens and thereby providing host protection while allow time for the more critical robust adaptive immunity to kick in.
Lactoferrin is an iron-binding glycoprotein most abundant in human milk and is found in mucosal secretions such as saliva, tears, nasal, gut and genital secretions (9). It is also found expressed and secreted by granules of the neutrophils (10). Therefore, it is a key component of the first line of host defence. Several clinical studies have provided evidence that oral administration of bovine lactoferrin is effective against microbial infections in patients with impaired immunity (11-14) through its ability to mobilize circulating neutrophils (15) and natural killer cells (16), modulate iron store (17), as well as regulate inflammatory cytokines (18). Thus by boosting the innate immune system which is defective in AD, patients could benefit from lactoferrin administration.
Polysaccharide-K (PSK), is a proteoglycan extracted from the mushroom Coriolus versicolor. PSK is an immunomodulator that has the ability to activate the immune system in healthy subjects (19) and to increase immune function in patients undergoing anticancer therapy (20). PSK has been reported to be effective in modifying the cells of the adaptive immunity from Th2 dominance to Th1 dominance through suppression of the production of Th2 cytokines (21). Thus, in patients with AD whose clinical activity is associated with a Th2 response, a shift to a protective Th1 immunity by taking PSK could be beneficial.
Based on scientific evidence, the combination of boosting the innate immune system and modifying the adaptive immunity with Immunostim could provide a novel approach to the treatment of atopic dermatitis.
