Overall, our results show that SIS models are capable of secreting more IL-6, IL-8, and TNFα when challenged by N. gonorrhoeae than Transwell® models, that SV-HUC-1 uroepithelial cells react more pronounced to infection than T84 or HEC-1-B cells, and that there are no major differences in cytokine levels produced in response to different gonococcal strains and derivatives. Here, TNF is linked to infection.