Viral respiratory infections and the maturation of nasal immune responses in infants: the VIGALL study

The human body has an extensive defence mechanism (immune system) for coping with pathogens. It is regulated by signalling molecules called cytokines. Cytokines are produced by various cells of the immune system such as leucocytes (e.g. T-cells and macrophages) but also by nasal and pulmonary epithelial tissue. There are several different types of cytokines. Th1 cytokines are involved in the eradication of bacterial and viral pathogens, while Th2 cytokines are involved in the defence against parasites. The production of Th1 cytokines is suppressed by Th2 cytokines and vice-versa so that the production of both cytokines is kept in balance. An overproduction of Th1 cytokines is found in auto-immune disorders, while allergic disease is frequently accompanied by high Th2 cytokine production. Furthermore, pro-inflammatory cytokines can induce general inflammatory reactions, while anti¬inflammatory and regulatory cytokines may downregulate these responses. Immune responses in newborns are immature. This is seen in relatively high levels of Th2 and regulatory cytokines and low levels of Th1 cytokines compared to adults. The infant immune system matures with age. This maturation process consists of a relative increase in the production of Th1 cytokines compared to Th2 cytokines. Viral respiratory infections in infants may stimulate immune matura¬tion by their repeated Th1 stimulating effect, and thereby reduce the risk of a child developing Th2-mediated allergic disease. This hypothesis was first proposed by Professor Strachan in 1989 and is known as the ’hygiene hypothesis’.In the VI¬GALL study (VIGALL is the Dutch abbreviation for virally-mediated allergy), we examined whether respiratory infections predominantly induced by viruses may affect the maturation of the immune system and the development of allergic dis¬ease. We therefore looked to see which respiratory viruses are most prevalent in infants and what types of immune response are induced in the nos

Predominance of rhinovirus in the nose of symptomatic and asymptomatic infants

Respiratory infections in infancy may protect against developing Th2-mediated allergic disease (hygiene hypothesis). To estimate the relative contribution of particular viruses to the development of the immune system and allergic disease, we investigated longitudinally the prevalence of respiratory viral infections in infants. One hundred and twenty-six healthy infants were included in this prospective birth cohort study in their first year of life. Physical examination was performed and nasal brush samples were taken during routine visits every 6 months and during an upper respiratory tract infection (URTI) (sick visits). The prevalence of respiratory viral infections in infants with URTI, infants with rhinitis without general malaise and infants without nasal symptoms was studied. Rhinovirus was the most prevalent pathogen during URTI and rhinitis in 0- to 2-year-old infants (similar to40%). During URTI, also respiratory syncytial virus (similar to20%) and coronavirus (similar to10%) infections were found, which were rarely detected in infants with rhinitis. Surprisingly, in 20% of infants who did not present with nasal symptoms, rhinovirus infections were also detected. During routine visits at 12 months, a higher prevalence of rhinovirus infections was found in infants who attended day-care compared with those who did not. We did not observe a relation between breast-feeding or smoking by one or both parents and the prevalence of rhinovirus infections. The parental history of atopy was not related to the prevalence of rhinovirus infection, indicating that the genetic risk of allergic disease does not seem to increase the chance of rhinovirus infections. In conclusion, rhinovirus infection is the most prevalent respiratory viral infection in infants. It may therefore affect the maturation of the immune system and the development of allergic disease considerabl