In conclusion, the present data reveals the possibility that SP acting via NK-1R initiates signaling cascade that is mediated by PKCα and leads to NF-κB and AP-1 activation and further modulates proinflammatory mediators in polymicrobial sepsis, and the effect of SP is blocked 8 hours after CLP by NK-1R antagonist SR140333 administered 30 minutes before and 1 hour after CLP. The gene discussed is JUN; the disease is Sepsis.