Both Very Low- and Very High In Vitro Cytokine Responses Were Associated with Infant Death in Low-Birth-Weight Children from Guinea Bissau: e93562

• Published in: PloS one 2014-04, Vol.9 (4)
• Main Authors: Andersen, Andreas, Jensen, Kristoffer J, Erikstrup, Christian, Ravn, Henrik, Fisker, Ane B, Lisse, Ida M, Sartono, Erliyani, Aaby, Peter, Yazdanbakhsh, Maria, Benn, Christine S
• Format: Article
• Language: English
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0093562

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-Guerin (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)- gamma , and tumor necrosis factor (TNF)- alpha 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- gamma responses to PPD were associated with better survival (MR ratio = 0.43 (0.24-0.77)). Conclusions 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.