134. Euflammation: Induction of robust inflammation without sickness behavior

Sickness behavior is a hallmark of inflammation. This has been validated by research using acute high dose endotoxin/bacterial challenges to simulate inflammation. To mimic natural infection, we examined the effects of repeated low dose Escherishia coli on sickness behavior and local peripheral inflammation. Results showed a behavioral dose response, where increased amounts of E. coli caused more severe sickness behavior. However, animals that were given a sub-threshold dose of E. coli 24 h prior were able withstand a larger dose of E. coli on the second day without causing sickness behavior. By using the same methodology, animals receiving escalating sub-threshold doses of E. coli on days 1 and 2 could behaviorally tolerate a dose of E. coli 50X higher than what would normally cause sickness behavior acutely. ELISA data for IL-6 and IL1-beta levels in the peritoneal cavity showed increasing levels of E. coli caused increased levels of both cytokines and these increases were diminished by giving a sub-threshold dose of E. coli 24 h prior. In addition, after a 3-day escalating E. coli challenge, phagocytic index to E.coli in peritoneal macrophages increased 11 times and animals were refractory to LPS induced sickness behavior if LPS was given after the E.coli challenges. Thus, progressive controlled stimulation of innate immune activity produced a robust sickness-free inflammation, which we term euflammation.