The Potential Role and Possible Immunological Mechanisms of Zinc Adjunctive Therapy for Severe Pneumonia in Children

ABSTRACT

Zinc deficiency is widespread and tends to mirror the distribution of infectious diseases prevalent in the developing world. Despite numerous observational studies suggesting a key role for zinc in human immunity and an involvement in disease pathogenesis, the underlying mechanisms remain poorly understood, and zinc intervention trials across a range of diseases have yielded mixed results. There is suggestive evidence that zinc supplementation may reduce initial susceptibility to pneumonia (i.e. preventive), but interpretation is confounded by the use of varied and imprecise diagnostic criteria. Evidence for a therapeutic (i.e. lower pneumonia severity and duration) effect of adjunctive zinc in preexisting disease is less secure and similarly confounded. In neither case has there been substantive research into the putative mechanisms by which zinc could be beneficial.

Animal studies suggest a beneficial role for zinc in T cell immunity; with deficiency resulting in involution of the thymus, which is the seat of T cell development. Here we review the evidence that zinc may play a critical role in human infectious diseases immunity through effects on T cell generation and mediation of cytokine production. Additional mechanisms may involve a role in the removal of metabolic toxins via free radical scavenger molecules for which zinc is an essential cofactor. We review the theory and existing evidence to support that zinc supplementation promotes the induction of T cell immunity to control infection and ameliorate immunopathology including excess inflammation. This is a potential route by which respiratory tissue regeneration may be achieved following respiratory tract infections in children benefiting from zinc adjunct therapy.