In summary, our findings show that the pre-incubation of P. gingivalis and F. nucleatum and subsequent infection of OKs induce significant increments in the expressions of IL-1β, IL-8, and TNF-α and a synergistic increase in the IL-6 expression compared to the monocultures of P. gingivalis and F. nucleatum and the co-infection. The gene discussed is IL1B; the disease is infection.