Pre-treatment of C57BL6/J mice with the TLR4 agonist monophosphoryl lipid A prevents LPS-induced sickness behaviors and elevations in dorsal hippocampus interleukin-1β, independent of interleukin-4 expression.

•MPLA administration can trigger expression of sickness behaviors in C57BL/6J mice.•Treatment with MPLA for two consecutive days prior to LPS administration is sufficient to prevent LPS-induced sickness behaviors.•Treatment with MPLA for two consecutive days prior to LPS administration is sufficient to prevent LPS-induced elevations in IL-1β in the dorsal hippocampus.•MPLA protection from LPS-induced sickness behaviors appears to be independent of effects on IL-4 expression in the dorsal hippocampus.