Early-Life Immune Insult and Developmental Immunotoxicity (DIT)-Associated Diseases: Potential of Herbal- and Fungal-Derived Medicinals

Developmental immunotoxicity (DIT) is increasingly recognized as a significant risk factor contributing to later life immune dysfunction as well chronic disease. In fact, recent increases in the incidence of asthma, allergic disease, autoimmunity and childhood infections maybe linked to problematic early life environmental exposures. The immune system of the non-adult is particularly susceptible to environmental influences whether from prenatal exposure to environmental toxins, maternallyadministered drugs, infections or from postnatal exposure to toxicants, infectious agents and allergens. Additionally, adultexposure models of immunotoxicity have been largely ineffective in predicting DIT risk. DIT-induced immune dysfunction can take many forms depending upon the environmental factor(s) involved and the precise developmental timing of exposure. If one examines the spectrum of published studies, a predominant phenotype has emerged that includes: Th balance skewing toward Th2, suppression of Th1 function, regulatory T cell function alteration, T cell repertoire abnormalities, problematic regulation of inflammatory cell function leading to hyperinflammatory responses and perturbation of cytokine networks. Early-life immune insult can also result in damage to the neurological and cardiovascular systems as well as endocrine and reproductive organs. Most therapeutic approaches to date have addressed the disease outcomes of DIT (e.g. asthma, allergy, autoimmunity, infections, and cancer) rather than focusing on the underlying immune dysfunction that creates the increased disease risk. While identification and prevention of problematic early life exposures is the best protection against DIT, this is not always possible. Therefore, identification of potential therapeutic approaches to reverse the immune dysfunction in the juvenile or adult is needed. In this review, we consider potential phytotherapeutic candidates among herbal- and fungal-derived medicinals for possible postnatal correction of the most predominant DIT-induced immune problems.