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Int J Infect Dis. 2013 Dec;17(12):e1186-93. doi: 10.1016/j.ijid.2013.07.006. Epub 2013 Sep 12.

Interleukin and neurotrophin up-regulation correlates with severity of H1N1 infection in children: a case-control study.

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Department of Pediatrics, Catholic University of the Sacred Heart, A. Gemelli Hospital, Largo Gemelli, 1, 00168, Rome, Italy. Electronic address:



To evaluate the correlation between cytokine and neurotrophin expression and clinical findings, disease severity, and outcome of children with H1N1 influenza infection.


A prospective observational clinical study was performed on 15 children with H1N1 infection, 15 controls with lower respiratory tract infections (LRTI), and 15 non-infected children. Plasma levels of interleukin (IL)-1β, IL-6, and neurotrophic factor (nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and glial derived neurotrophic factor (GDNF)) were measured using immunoenzymatic assays.


Significantly higher levels of IL-1β, IL-6, BDNF, and NGF were detected in patients with H1N1 infection compared to LRTI controls, while there was no significant variation in GDNF in the two groups. IL-1β, IL-6, BDNF, and NGF levels were significantly higher in H1N1 patients with more severe clinical manifestations compared to H1N1 patients with mild clinical manifestations. Of note, IL-6 was significantly correlated with the severity of respiratory compromise and fever, while NGF up-regulation was associated with the duration of cough. No correlation was found between interleukin and neurotrophic factor expression and outcome.


H1N1 infection induces an early and significant IL-1β, IL-6, BDNF, and NGF up-regulation. The over-expression of these molecular markers is likely to play a neuroimmunomodulatory role in H1N1 infection and may contribute to airway inflammation and bronchial hyper-reactivity in infected children.


Brain derived neurotrophic factor; Glial derived neurotrophic factor; H1N1 influenza; Interleukins; Nerve growth factor

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