H. J. Neijens

Type 1-like immune response is found in children with respiratory syncytial virus infection regardless of clinical severity

The immunological response of infants younger than six months to infection with respiratory syncytial virus (RSV) was studied in relation to clinical severity. IL‐6 and IL‐8 were found more frequently and at higher levels in the plasma samples of more severely ill patients and no significant differences were found in the levels of cytokines differentiating between Type 1 and Type 2 responses. Cellular infiltrates in nasopharyngeal washings consisted mainly of polymorphonuclear granulocytes and monocytes. Eosinophils, IgE positive cells and tryptase positive cells were found sporadically. Analyses of RSV stimulated T cell cultures established from peripheral blood mononuclear cells, for intracellular and secreted cytokines showed that, irrespective of clinical severity, the responses were dominated by the production of IFN‐γ, and that only low levels of IL‐4 and IL‐10 were detectable. Collectively these data do not indicate an association between clinical severity and a Type 2‐like T cell response. J. Med. Virol. 62:267–277, 2000.

Timing of Infection and Prior Immunization with Respiratory Syncytial Virus (RSV) in RSV-Enhanced Allergic Inflammation

Respiratory syncytial virus (RSV) infection has been shown to be a risk factor for the development of allergy in humans and mice. The allergy-enhancing properties of RSV may be dependent on atopic background and an individuals history of RSV infection. We examined the influence of the timing of infection and prior inoculation with RSV in a mouse model of allergic asthma. Mice were sensitized to and challenged with ovalbumin (OVA) and were inoculated with RSV either before or during the sensitization or challenge period. One group of mice was inoculated with RSV both before sensitization to OVA and during challenge with OVA. Increased pulmonary expression of interleukin (IL)-4, IL-5, and IL-13 mRNA and aggravated alveolitis and hypertrophy of mucus-producing cells were observed only when OVA-sensitized mice were inoculated with RSV shortly before or during challenge with OVA. Despite protection against viral replication, prior inoculation with RSV did not abrogate RSV-enhanced, OVA-induced expression of T helper 2 (Th2) cytokines in the lung. In conclusion, inoculation with RSV enhances allergic disease only when the immune system has already been Th2-primed by the allergen (i.e., OVA). This RSV-enhanced allergy is not completely abrogated by prior inoculation with RSV.

Respiratory syncytial virus, pneumonia virus of mice, and influenza A virus differently affect respiratory allergy in mice

Background Respiratory viral infections in early childhood may interact with the immune system and modify allergen sensitization and/or allergic manifestations. In mice, respiratory syncytial virus (RSV) infection during allergic provocation aggravates the allergic T helper (Th) 2 immune response, characterized by the production of IL‐4, IL‐5, and IL‐13, and inflammatory infiltrates. However, it is unclear whether the RSV‐enhanced respiratory allergic response is a result of non‐specific virus‐induced damage of the lung, or virus‐specific immune responses.

Influence of respiratory syncytial virus infection on cytokine and inflammatory responses in allergic mice

Background Th2 lymphocyte responses are associated with inflammation and disease during allergic responses. Exposure to particular environmental factors during the expression of allergy could result in more pronounced Th2‐like immune responses and more severe disease. One factor might be a respiratory virus infection.

RSV‐induced bronchiolitis but not upper respiratory tract infection is accompanied by an increased nasal IL‐18 response

The aim of this study was to investigate potential differences in the local nasal immune response between bronchiolitis and upper respiratory tract infection induced by respiratory syncytial virus (RSV). Nasal brush samples were obtained from 14 infants with RSV bronchiolitis and from 8 infants with RSV upper respiratory tract infection. The samples were taken during infection (acute phase) and 2–4 weeks later (convalescent phase). Cytospin preparations were stained immunohistochemically for T cells, macrophages, and eosinophils. Staining also took place for intercellular adhesion molecule‐1 (ICAM‐1), T‐helper 1 (Th1)‐like (interleukin‐12 [IL‐12], interferon‐γ [IFN‐γ]), Th2‐like (IL‐4, IL‐10), and proinflammatory cytokines (IL‐6, IL‐8, IL‐18). During both RSV‐induced bronchiolitis and upper respiratory tract infection, cellular inflammation was observed. This was characterised by an increase in the numbers of nasal macrophages, which tended to be higher in bronchiolitis than in upper respiratory tract infection. Numbers of T lymphocytes and ICAM‐1 positive cells increased during both bronchiolitis and upper respiratory tract infection. There were no differences between numbers in the groups. Interestingly, a distinct nasal proinflammatory cytokine response was observed in RSV‐induced bronchiolitis. This is characterised by an increase in the number of IL‐18 positive cells. This increase is specific for bronchiolitis, as a similar increase could not be detected in RSV‐induced upper respiratory tract infection. Numbers of IL‐6 and IL‐12 positive cells were higher in both bronchiolitis and upper respiratory tract infection, and there were no differences between the groups. By contrast, the number of IL‐8, IFN‐γ, IL‐4, and IL‐10‐positive cells remained constant. In conclusion, clear differences were found in nasal immune responses of children with RSV‐induced upper respiratory tract infection or bronchiolitis. The induction of a strong IL‐18 response was typical for bronchiolitis, as this could not be observed in RSV‐induced upper respiratory tract infection, and could explain the eosinophilia that is observed frequently during bronchiolitis. J. Med. Virol. 71:290–297, 2003.

Prolonged nasal eosinophilia in allergic patients after common cold

Background:u2002Viral respiratory tract infections may cause both harmless common colds and severe asthma exacerbations; the differences in disease expression probably depend on the all_ergic status of the patient. To determine whether altered immunologic mechanisms underlie these differences, we investigated nasal inflammation during naturall_y acquired common cold.

Reduced nasal IL-10 and enhanced TNFα responses during rhinovirus and RSV-induced upper respiratory tract infection in atopic and non-atopic infants

Rhinovirus and respiratory syncytial virus (RSV) are the most prevalent inducers of upper respiratory tract infections (URTI) in infants and may stimulate immune maturation. To estimate the amount of immune stimulation, nasal immune responses were examined during rhinovirus and RSV‐induced URTI in infants. Nasal brush samples were taken from infants (2–26 months; 57% atopic family) with rhinovirus‐induced URTI (Nu2009=u200920), with RSV‐induced URTI (Nu2009=u20097), and with rhinovirus‐induced rhinitis (Nu2009=u200911), from children with asymptomatic rhinovirus infection (Nu2009=u20097) and from eight non‐infected children. Numbers of nasal brush cells positive for Th1‐, Th2‐, regulatory and proinflammatory cytokines were measured by immunohistochemistry or by measuring protein levels using a cytometric bead array analysis. During rhinovirus and RSV‐induced URTI, fewer regulatory cytokine IL‐10 positive cells were found compared to non‐infected children. This fall was accompanied by an increase in levels of the Th1 cytokine TNFα. IL‐10 responses were inversely related to TNFα responses. No enhanced responses were observed for IFNγ, IL‐12 and IL‐18. Cytokine responses were comparable in children with rhinovirus‐induced URTI and in children with rhinitis, while responses in asymptomatic rhinovirus‐infected children were located between those for symptomatic and asymptomatic rhinovirus‐infected children. Cytokine responses did not depend on the age of the child or atopy in the family. In conclusion, reduced nasal IL‐10 responses during URTI in infants could facilitate the induction of a TNFα response. TNFα in turn could replace the immature production of IL‐12, IL‐18 and IFNγ during URTI to induce an effective clearance of the viral infection and which could stimulate the maturation of Th1 cytokine production in infancy. J. Med. Virol. 75:348–357, 2005.

Age- and infection-related maturation of the nasal immune response in 0-2-year-old children

Background:u2002 The hygiene hypothesis suggests that exposure to micro‐organisms influences development of the immune system in children.