Mar 6, 2012

Early Exposure to Infections or Microbial Products?

One hypothesis that has attracted considerable interest is that a decline in certain childhood infections or a lack of exposure to infectious agents during the first years of life associated with smaller families in the middle class environments of industrialized countries may be causal for the recent epidemic in atopic disease and asthma. Although this hypothesis is obviously very complex, various sources of information appear to support it. Studies from several countries provide indirect evidence for the hypothesis that early exposure to viral infections, although triggering lower airway symptoms during early life, may exert long-lasting protective effects. Children born into families with several siblings, especially older siblings, have been found to have reduced risk of allergic sensitization and asthma at school age. Studies in children who attended day-care centers during infancy support this concept. Infections are known to produce long-lasting nonspecific systemic effects on the nature of the immune response to antigens and
allergens. For example, recovery from natural measles infection reduces the incidence of atopy and allergic responses to house dust mites to half the rate found in vaccinated children.
Obviously, the fact that certain infections induce a systemic and nonspecific switch to Th1 cells may be responsible for inhibiting the development of atopy during childhood.

Observations from Japan suggesting that strong positive tuberculin responses in children predict a lower incidence of asthma, lower serum IgE levels, and cytokine profiles biased toward a Th1-type were supported by animal experiments demonstrating that IgE responses to ovalbumin in mice could be down-regulated by a previous infection with bacillus Calmette-Guerin (BCG).
Unfortunately, cohort studies from Europe were unable to describe any protective
effect of BCG vaccination.
Although these observations on the relationship of immune responses to infectious agents, atopic sensitization, and disease expression are stimulating and challenging, conclusions regarding the relevance of the atopic march should be drawn with care.

In different parts of the world, completely different infectious agents have been addressed in different study settings. It appears to be fashionable to join Rook and Stanford who, in a recent review article pleaded “Give us this day our daily germs”—but which germ, at what time, under which circumstances, and at what price?

No comments: