Changes in helper lymphocyte chemokine receptor expression and elevation of IP-10 during acute respiratory syncytial virus infection in infants.

It is known that lymphopenia caused by apoptosis may occur during severe respiratory syncytial virus (RSV) infection. However, further evidence about how T-cell subsets may be affected in infants during severe RSV bronchiolitis is needed to understand the mechanisms through which immunological memory may be altered. There is increasingly convincing evidence that RSV may be associated with the development of atopy and asthma. Surrogates of Th1, Th2 and regulatory T-lymphocyte populations were measured in blood from children with acute RSV bronchiolitis and in convalescence using the cell surface receptors CXCR3, CCR4 and CD25, respectively. Samples were also obtained from healthy age-matched controls. Plasma levels of the chemokines interferon-γ inducible protein-10 (IP-10) and thymus and activation-regulated chemokine (TARC), which are known ligands for CXCR3 and CCR4, were also measured. Free plasma DNA was measured using quantitative PCR. CXCR3-positive cells were significantly decreased during acute infection (p = 0.013), while CCR4 and CD25 T-cell populations were unchanged. Plasma levels of IP-10 were markedly elevated in acute infection (p = 0.001). Convalescent samples were not significantly different to control samples for lymphocyte phenotypes or plasma chemokines. Elevated free plasma DNA was detected during acute infection compared with convalescence and controls. A profound reduction in the Th1, but not Th2, and CD25-positive lymphocyte populations associated with exaggerated IP-10 production occurs in severe RSV bronchiolitis. Free DNA is detectable in plasma. This may allow significant alterations in the generation of T-cell memory.

The neuroendocrine stress response and severity of acute respiratory syncytial virus bronchiolitis in infancy.

OBJECTIVE: Neuroendocrine hormones have profound effects on the immune system. The immune response is a major factor in the pathogenesis of acute respiratory syncytial virus (RSV) infection. We hypothesised that there is a relationship between the neuroendocrine response in acute RSV infection, the severity of illness, and the degree of lymphopenia. DESIGN: Prospective, non-randomised cohort study of infants hospitalised for RSV infection requiring mechanical ventilation or managed conservatively. The study assessed the effect of age, gender, birth gestation, and severity of illness on stress hormone profile and its relationship to lymphocyte count. SETTING: Regional Paediatric Intensive Care Unit (PICU) and children's wards. PATIENTS: Thirty-two consecutive infants with RSV infection were enrolled, of which thirteen were mechanically ventilated on PICU (study subjects) and nineteen treated on the ward (comparison group). Twenty-three children (72%) returned for follow-up. MEASUREMENTS AND MAIN RESULTS: A specific neuroendocrine profile was found in PICU patients compared to ward patients (Wilks Lambda = 0.36, F = 9.05, P =.03). PICU patients had significantly higher prolactin and growth hormone, and significantly lower leptin and IGF-1. Cortisol levels were the same. PICU patients were more lymphopenic compared to ward patients (P =.0001). On multiple regression analysis, prolactin and leptin levels accounted for 57% of the variation in lymphocyte count. CONCLUSIONS: Whereas the effect of intensive care (mechanical ventilation and medication) could not be controlled for, our results suggest that there is an association between the neuroendocrine hormone response, severity of illness and degree of lymphopenia.