Cytokine response after severe respiratory syncytial virus bronchiolitis in early life

Abstract

Background Immune response following viral infection usually involves Th1-mediated response; however, severe respiratory syncytial virus (RSV) infection appears to be associated with the development of asthma, a Th2-predominant phenotype. Objective To understand the early and subsequent immunologic response to a serious RSV infection in children over time. Methods 206 previously healthy infants hospitalized with severe RSV bronchiolitis were enrolled in a prospective cohort called the RSV Bronchiolitis in Early Life (RBEL) study. Peripheral blood T cells were obtained immediately following RSV infection and at 2, 4 and 6 years of age, stimulated with PMA and ionomycin, and analyzed for interleukin (IL)-2, -4, and - 13 and interferon-γ (IFN-γ) by flow cytometry and real time PCR. Results 48% (n=97) of the children developed asthma (physician-diagnosed) and 48% (n=97) had eczema by age 6. 32% (n=48 of 150) developed allergic sensitization by 3 yrs of age. Children with asthma had lower IL-13 expression at 6 yrs of age than those without (p=0.001). IFN-γ, IL-2 and -4 levels did not differ by asthma or eczema status during follow-up (all p>0.05). Allergic sensitization was not associated with differences in cytokine levels during follow-up (all p>0.05). Conclusion Severe RSV infection early in life is associated with a high incidence of asthma and eczema. Contrary to expectations, subsequent immunologic development in those who developed asthma, eczema or allergic sensitization was not associated with a Th2 phenotype in the peripheral blood.

Asthma as a chronic disease of the innate and adaptive immune systems responding to viruses and allergens

“…The first of these stems from the role of innate immunity in host defense against inhaled and/or aspirated pathogens. Circumstantial evidence indicates a direct relationship between viral level and both the severity of acute illness and the likelihood of chronic disease (12,133,134). In fact, the capacity of the host to control viral level may be deficient in asthma.…”

“…Early clinical work on the role of respiratory viruses in asthma focused on the role of respiratory syncytial virus (RSV) infection in infancy. RSV is the most common cause of serious respiratory illness in this age group and in severe cases is associated with the subsequent development of a prolonged wheezing illness that in some cases may extend at least to adolescence (9)(10)(11)(12)(13)(14)(15)(16). The role of severe RSV infection as a risk factor for asthma in adulthood is less certain but is still under study.…”

Recurrence of Wheezing Episodes in Children with Respiratory Syncytial Virus and Non-Respiratory Syncytial Virus Bronchiolitis

“…31 We co uld not study the vi ral eti o logy in that study but we sup po sed that RSV had be en the ca u sa ti ve agent in the ma jo rity of cases. In the study of Cas tro et al 32 206 in fants we re fol lo wed up af ter a se ve re RSV in fec ti on, and IL-2, IL-4, IL-13 and IFN-γ we re stu di ed im me di a tely af ter the in fec ti on, at the age of 2, 4 and 6. The authors fo und that IL-13 ex pres si on was lo wer in the gro up of in fants who de ve lo ped ast hma la ter and de ni ed the ro le of Th2 type im mu ne res pon se in de ve lop ment of ast hma af ter RSV in fec ti on.…”

Challenges and Opportunities for Respiratory Syncytial Virus Vaccines

“…(Bacharier et al, 2012) Interestingly, when peripheral blood was drawn from the children diagnosed with asthma at age 6, the isolated T cells had decreased IL-13 expression following phorbol 12-myristate 13-acetate (PMA) and ionomycin stimulation compared to those without asthma. (Castro et al, 2008) While severe RSV bronchiolitis has been linked to the development of asthma later in life, it is possible that the severe RSV infection is not causative of asthma, but instead a marker of the true risk factor for asthma. This possibility was investigated in the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC 2000 ) cohort, a prospective clinical study of a birth cohort of 411 neonates born to mothers with a history of asthma.…”