Cytokine responses in cord blood predict the severity of later respiratory syncytial virus infection

Juntti, Hanna; Österlund, Pamela; Kokkonen, Jorma; Dunder, Teija; Renko, Marjo; Pokka, Tytti; Julkunen, Ilkka; Uhari, Matti

doi:10.1016/j.jaci.2009.04.014

Cited by 34 publications

(35 citation statements)

References 41 publications

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“…Preterm human infants can exhibit severe responses to infections such as RSV (13), which has been linked to increased inflammatory cytokines in cord blood (14). Consistent with this, in the present study, we observed exaggerated inflammatory cellular responses to SeV lung challenge in LPS-exposed pups relative to infected neonates without such exposure.…”

Section: Discussionsupporting

confidence: 90%

“…Paradoxically, clinical and experimental observations suggest that even preterm neonates can mount exaggerated inflammatory responses to infectious stimuli that could contribute to chronic morbidity or mortality (13)(14)(15)(16)(17). The mechanisms underlying this "hyper-inflammatory" phenotype are not well understood, although some evidence implicates impaired innate and adaptive immune interactions that disrupt homeostatic balance (7).…”

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confidence: 99%

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Maternal inflammation modulates infant immune response patterns to viral lung challenge in a murine model

et al. 2014

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Background: Chorioamnionitis, an inflammatory gestational disorder, commonly precedes preterm delivery. Preterm infants may be at particular risk for inflammation-related morbidity related to infection, although the pathogenic mechanisms are unclear. We hypothesized that maternal inflammation modulates immune programming to drive postnatal inflammatory processes. Methods: We used a novel combined murine model to treat late gestation dams with low-dose lipopolysaccharide (LPS) and to secondarily challenge exposed neonates or weanlings with Sendai virus (SeV) lung infection. Multiple organs were analyzed to characterize age-specific postnatal immune and inflammatory responses. results: Maternal LPS treatment enhanced innate immune populations in the lungs, livers, and/or spleens of exposed neonates or weanlings. Secondary lung SeV infection variably affected neutrophil, macrophage, and dendritic cell proportions in multiple organs of exposed pups. Neonatal lung infection induced brain interleukin (IL)-4 expression, although this response was muted in LPS-exposed pups. Adaptive immune cells, including lung, lymph node, and thymic lymphocytes and lung CD4 cells expressing FoxP3, interferon (IFN)-γ, or IL-17, were variably prominent in LPS-exposed pups. conclusion: Maternal inflammation modifies postnatal immunity and augments systemic inflammatory responses to viral lung infection in an age-specific manner. We speculate that inflammatory modulation of the developing immune system contributes to chronic morbidity and mortality in preterm infants. c horioamnionitis, an antenatal inflammatory disorder, is detected in the majority of placentas following extremely preterm delivery (1). The resultant fetal inflammation has been associated with postnatal development of chronic inflammatory disorders, including retinopathy of prematurity, periventricular leukomalacia, bronchopulmonary dysplasia, and necrotizing enterocolitis (2-4). However, the pathogenic role of chorioamnionitis in neonatal morbidity, particularly regarding

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Section: Discussionsupporting

confidence: 90%

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confidence: 99%

Maternal inflammation modulates infant immune response patterns to viral lung challenge in a murine model

et al. 2014

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“…Infection of DCs, macrophages, and peripheral blood mononuclear cells with RSV induced secretion of IL-6 (19). High IL-6 responsiveness predicted a severe RSV infection in children (19). In the current study, although the RSV load in lungs was dramatically suppressed, the levels of IL-6 mRNA were still high in all experimental groups except the pIL-27ϩG1F/M2 group.…”

Section: Humoral Immune Response Induced By Pil-27؉g1f/m2mentioning

confidence: 39%

“…Infection of DCs, macrophages, and peripheral blood mononuclear cells with RSV induced secretion of IL-6 (19). High IL-6 responsiveness predicted a severe RSV infection in children (19).…”

Section: Humoral Immune Response Induced By Pil-27؉g1f/m2mentioning

confidence: 99%

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Interleukin-27 Inhibits Vaccine-Enhanced Pulmonary Disease following Respiratory Syncytial Virus Infection by Regulating Cellular Memory Responses

Zeng

Zhang

Yan

et al. 2012

J Virol

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Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract disease in infants and young children, accounting for approximately 5% of hospitalizations due to lower respiratory tract infections (15). Premature infants, immunocompromised individuals, and the elderly are the populations at the greatest risk to develop life-threatening RSV infections (10, 29). Moreover, reinfections occur frequently during life due to incomplete immunity after RSV infection. A number of clinical epidemiology studies have identified that there is a strong association between RSV bronchiolitis in infancy and the development of wheezing and asthma in later childhood (31,36,37). The World Health Organization has established a high priority for the development of an RSV vaccine. However, efforts to develop a safe and effective vaccine have been unsuccessful. In the 1960s, a formalininactivated RSV (FI-RSV) vaccine was used to immunize infants; these infants developed a more severe disease upon natural RSV infection; 80% of them but only 5% of infants that received a control vaccine required hospitalization, and two died (21). Histology performed on the lungs of the deceased revealed extensive neutrophils, mononuclear cells, and lymphocytes and increased numbers of eosinophils infiltrating the lungs (33).Although the vaccine-enhanced disease (VED) is a major concern in the development of a safe and effective RSV vaccine, its immunological mechanisms are unclear. Many pieces of evidence showed that VED was associated with an exaggerated Th2-type response. Depletion of Th2 cytokine interlukin-4 (IL-4) or IL-13 of mice immunized with FI-RSV inhibited the development of pulmonary disease after RSV challenge (18). The Th2 polarization may have been related to the absence of a Th1-promoting RSVspecific cytotoxic T lymphocyte (CTL) response after immunization with FI-RSV (29). RSV challenge of FI-RSV-immunized mice elicited a robust memory CD4 ϩ T cell response in the absence of a detectable memory CD8 ϩ T cell response, pulmonary eosinophilia, and VED (29). Immunization of BALB/c mice with a recombinant vaccinia virus (vacv) that expresses the RSV M2 protein (vacvM2) elicited an RSV-specific memory CD8 ϩ T cell response. Mice coimmunized with FI-RSV and vacvM2 after RSV challenge did not develop pulmonary eosinophilia, along with downregulation of pulmonary Th2 cytokines and upregulation of Th1 cytokines (41). Despite the beneficial role, Th1-biased or CD8 ϩ T-biased cellular memory may also be detrimental to the host. RSV challenge of mice previously immunized with vacv expressing the RSV F protein (vacvF) exhibited a memory Th1 response in the absence of a detectable memory Th2 response and developed lung inflammation characterized by mononuclear cell infiltration (5,17,28). In the mice immunized with vacvM2 or vacvF, systemic disease, including weight loss, occurs after RSV challenge, although no eosinophilia was detectable (5,17,28). These data clearly suggested that both a Th2 memory response and a Th1 or CD8 ϩ...

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IL-10gene polymorphism is associated with preschool atopy and early-life recurrent wheezing after bronchiolitis in infancy

et al. 2016

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Cytokine responses in cord blood predict the severity of later respiratory syncytial virus infection

Cited by 34 publications

References 41 publications

Maternal inflammation modulates infant immune response patterns to viral lung challenge in a murine model

Maternal inflammation modulates infant immune response patterns to viral lung challenge in a murine model

Interleukin-27 Inhibits Vaccine-Enhanced Pulmonary Disease following Respiratory Syncytial Virus Infection by Regulating Cellular Memory Responses

IL-10gene polymorphism is associated with preschool atopy and early-life recurrent wheezing after bronchiolitis in infancy

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