Prescribing beyond the usual suspects in immune support can help to expand therapeutic potentials and offer a more targeted and individual approach. Prescribing proteolytic enzymes, factoring in the multifaceted roles of retinoic acid, and modulating the immune system indirectly with cholecalciferol via the antimicrobial barrier of the mucosa, are just some of the ways we can take a more considered and comprehensive approach.

Proteolytic enzymes such as papain may be effective treatment adjuncts in congestive respiratory disorders such as rhinitis and sinusitis and their effect is thought to me mediated by thinning mucous secretions, breaking up immune complexes and providing anti-inflammatory activity.1 It is also suggested that systemic enzyme therapy may be of benefit in certain rheumatic disease. The precise mechanism is not fully understood but preliminary evidence suggests that orally administered proteases exert a regulatory effect on the cytokine network including Th1/Th2 cytokine balance.2

Upon its discovery, Vitamin A was known as the anti-infective vitamin and subsequent research has found vitamin A to have a broad impact on diverse aspects of the immune system, both directly and indirectly through its effects on epithelial barrier integrity.3 Retinoids are essential for the maintenance of healthy immune function, which depends on cell differentiation and proliferation in response to immune stimuli. Retinoic acid:4

• Is important for maintaining circulating concentrations of NK cells which have anti-viral and anti-tumour activity
• Increases phagocytic activity
• Increases production of IL-1 and other cytokines
• Mediates inflammation
• Stimulates T cell production
• Is required for the growth, differentiation and activation of B lymphocytes.

Deficiency of vitamin A is associated with increased risk of infections including respiratory infections and supplementation has been shown to reduce the severity of diarrhoea and malaria infections in young children.4

Vitamin A induced conversion of naïve T cells in the gut-associated lymphoid tissue to regulatory T cells cells are thought to account for the development of appropriate immune-tolerance. Regulatory T cells are responsible for inducing and maintaining peripheral tolerance to compounds such as dietary or environmental antigens. Retinoic acid also sustains the stability and function of Treg cells during inflammation and induces the expression of gut-homing receptors allowing for the preferential tracking of Treg cells to specific tissue sites.3

Recent evidence suggests that retinoic acid also enhances immune tolerance by promoting T cell activation and T helper cell differentiation into different T helper subsets such as Th1, Th2 and Th17 cells.3

Vitamin A also assists with healthy immune system function by helping to maintain the integrity of epithelial surfaces throughout the body. Activation of retinoic acid and retinoid X receptors in the nucleus regulates the expression of genes that encode for structural proteins.4 The epithelial barrier is at the front line of mucosal immunity and barrier integrity is essential for protecting against infection, atopy and autoimmunity.5-10 The bodies epithelial barriers separates the host from environmental toxins, antigens, bacteria and viruses and a compromised barrier is known to have a myriad of consequences depending on the aggravating agents and the location in the body.9

Vitamin A may therefore be useful in clinical presentations as eczema, asthma, allergic rhinitis, respiratory and genitourinary infections, food sensitivities and autoimmunity.

The vitamin D receptor (VDR) plays a vital role in immune modulation, cellular differentiation, mitosis and suppression of the inflammatory response by decreasing IL-6, IL-2, and IL-23. The VDR is present in practically all immune cells. Vitamin D is also though to modulate the immune system indirectly by influencing the antimicrobial barrier of the mucosa, favourably altering the composition of the gut microflora and therefore barrier function and antigen presentation.11

Vitamin A and Vitamin D also work in synergy to regulate immune function with retinol playing a crucial role in the vitamin D pathway. The vitamin D receptor must form a heterodimer complex with retinoid X receptor to regulate gene transcription.12

Full reference list available upon request.