Abstract

Background: Coagulase-negative staphylococci (CoNS) are the most prevalent pathogens causing late-onset sepsis, and gestational age is the most important risk factor for these infections.

Objective: To characterize innate immune responses to S. epidermidis by assessment of whole blood in vitro cytokine production in a large group of preterm and term infants.

Results: The S. epidermidis-induced in vitro production of pro-inflammatory cytokines such as intracytoplasmatic IL-6 and TNF- in cord blood samples was found to be dependent on gestational age (R=0.279, p=0.002; R=0.251, p=0.005, respectively; n=121). In contrast, the production of anti-inflammatory cytokines such as IL-10 and TGF-ß was not associated with gestational age. Comparing different stimulation strategies, a strong correlation was noted for cytokine responses after lipopolysaccharide (LPS) and S. epidermidis exposure, i.e. IL-6 (R=0.431, p<0.001, n=161) and IL-10 (R=0.332, p<0.001, n=161). In addition, a lower IL-6 production was found in supernatants of whole blood cultures infected with a clinically isolated IcaABD positive (biofilm production) strain compared to a control IcaABD negative ATCC strain (p=0.009).

Conclusions:Our in vitro data suggest that pro-inflammatory responses to S. epidermidis are dependent on gestational age in preterm infants, while counteracting anti-inflammatory response to S. epidermidis might not be directly related to gestational age. Individual host factors may play a role as well as bacterial determinants, such as biofilm production. Further studies are encouraged to investigate the different aspects of innate immune responses to CoNS in the vivo situation.