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Abstract


Andersen A, Jensen KJ, Erikstrup C, Ravn H, Fisker AB, Lisse IM, Sartono E, Aaby P, Yazdanbakhsh M, Benn CS. Both very low- and very high in vitro cytokine responses were associated with infant death in low-birth-weight children from Guinea Bissau. Plose One. 2014 Apr 8;9(4):e93562. doi: 10.1371/journal.pone.0093562. eCollection 2

Background. The mechanisms behind heterologous immunity and non-specific effects of vaccines on mortality are not well understood. We examined associations between cytokine responses and subsequent mortality in low-birth-weight infants in Guinea-Bissau.

Methods. A low-birth-weight trial randomized children to Bacille Calmette-Guérin (BCG) at birth or later according to local policy. Blood samples were obtained from a sub-group at age 6 weeks. Interleukin (IL)-5, IL-10, IL-13, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were measured in whole-blood cell cultures stimulated with lipopolysaccharide (LPS), phytohaemagglutinin (PHA), or purified protein derivative (PPD). The outcome was mortality between bleeding and 1 year of age. Non-linear associations between cytokine responses and mortality were examined.

Results. Cytokine measurements were available from 390 children. The mortality rate (MR) was high (6.8/100 person-years-observation (PYO)). Both low and high cytokine responses to LPS and PHA were associated with high mortality (MR up to 25/100 PYO in the lowest 10% and 9.2/100 PYO in the highest 10%). In BCG-vaccinated children, higher IFN-γ responses to PPD were associated with better survival (MR ratio = 0.43 (0.24-0.77)).

Conlusions. Data presented a rare opportunity to explore associations between cytokine responses and mortality. Both low and high cytokine responses were associated with high mortality; a balanced response to invading pathogens seems preferable.


 

 

 

 

 

 

 

 

 

 

 

Last revised 11 April 2014