Epidemic influenza and vitamin D

Abstract

In 1981, R. Edgar Hope-Simpson proposed that a 'seasonal stimulus' intimately associated with solar radiation explained the remarkable seasonality of epidemic influenza. Solar radiation triggers robust seasonal vitamin D production in the skin; vitamin D deficiency is common in the winter, and activated vitamin D, 1,25(OH)2D, a steroid hormone, has profound effects on human immunity. 1,25(OH)2D acts as an immune system modulator, preventing excessive expression of inflammatory cytokines and increasing the 'oxidative burst' potential of macrophages. Perhaps most importantly, it dramatically stimulates the expression of potent anti-microbial peptides, which exist in neutrophils, monocytes, natural killer cells, and in epithelial cells lining the respiratory tract where they play a major role in protecting the lung from infection. Volunteers inoculated with live attenuated influenza virus are more likely to develop fever and serological evidence of an immune response in the winter. Vitamin D deficiency predisposes children to respiratory infections. Ultraviolet radiation (either from artificial sources or from sunlight) reduces the incidence of viral respiratory infections, as does cod liver oil (which contains vitamin D). An interventional study showed that vitamin D reduces the incidence of respiratory infections in children. We conclude that vitamin D, or lack of it, may be Hope-Simpson's 'seasonal stimulus'.

Fig. 1

The seasonal and latitudinal distribution of outbreaks of type A influenza in the world, 1964–1975, summarized from the Weekly Epidemiological Record of the World Health Organization into major zones. The diagrams show for each calendar month the percentage of each zone's total outbreaks. In both north and south temperate zones the epidemics are distributed around the local midwinter, whereas the tropical zones show a transition, each approximating towards the distribution of its own temperate zone. The curve indicates the ‘midsummer’ path taken annually by vertical solar radiation. The ‘epidemic path’ seems to parallel it, but to lag 6 months behind it. (Reproduced with permission, Cambridge University Press, Hope-Simpson, 1981.)

Fig. 2

Weekly consultation rates for illnesses diagnosed clinically as influenza or influenza-like, calculated from returns to the General Practice Research Unit of the Royal College of General Practitioners from about 40 general practices in various parts of England, Scotland and Wales, serving a population of about 150 000 persons, 1968–1970. (Reproduced/amended with permission, BMJ Publishing Group, Miller et al.)

Fig. 3

Seasonal variation of 25(OH)D levels in a population-based sample of inhabitants of a small southern German town, aged 50–80 years. (Reproduced/amended with kind permission of Springer Science and Business Media, Scharla, S.H., 1998.)