Abstract
We found recently that controlled progressive challenge with subthreshold levels of E. coli can confer progressively stronger resistance to future reinfection-induced sickness behavior to the host. We have termed this type of inflammation "euflammation". In this study, we further characterized the kinetic changes in the behavior, immunological, and neuroendocrine aspects of euflammation. Results show euflammatory animals only display transient and subtle sickness behaviors of anorexia, adipsia, and anhedonia upon a later infectious challenge which would have caused much more severe and longer lasting sickness behavior if given without prior euflammatory challenges. Similarly, infectious challenge-induced corticosterone secretion was greatly ameliorated in euflammatory animals. At the site of E.coli priming injections, which we termed euflammation induction locus (EIL), innate immune cells displayed a partial endotoxin tolerant phenotype with reduced expression of innate activation markers and muted inflammatory cytokine expression upon ex vivo LPS stimulation, whereas innate immune cells outside EIL displayed largely opposite characteristics. Bacterial clearance function, however, was enhanced both inside and outside EIL. Finally, sickness induction by an infectious challenge placed outside the EIL was also abrogated. These results suggest euflammation could be used as an efficient method to "train" the innate immune system to resist the consequences of future infectious/inflammatory challenges.