Genital infection with Neisseria gonorrhoeae (gonorrhea) is a significant cause of reproductive tract morbidity in women, leading to pelvic inflammatory disease, tubal factor infertility, and increased risk for ectopic pregnancy. WHO estimates that 78 million new infections occur annually worldwide. In the United States, >350,000 cases are reported annually, but the true incidence is probably >800,000 cases/year. Increasing resistance to currently available antibiotics raises concern that gonorrhea might become untreatable. Infection does not induce a state of immune protection against reinfection. Previous studies have shown that N. gonorrhoeae suppresses the development of adaptive immune responses by mechanisms dependent on the regulatory cytokines TGF-β and IL-10. This study shows that intravaginal treatment of gonococcal infection in female mice with microencapsulated IL-12 induces persisting anamnestic immunity against reinfection with N. gonorrhoeae, even of antigenically diverse strains, dependent on T-cell production of IFN-γ and B-cell production of antibodies.

An oral sustained-release formulation of Interleukin-10 suppressed tumor growth and enhanced survival in the APC/ spontaneous colon cancer model. Therapeutic benefit was associated with a 5-fold reduction in CD4RORγtFoxp3IL-17 T-helper cell, CD4RORγtFoxp3IL-17 pathogenic T-regulatory cell and CD4RORγtFoxp3IL-17 conventional T-regulatory cell numbers and a concurrent 2-fold enhancement in CD8 T-cell activity in the colon. Selective subset depletion and functional blockade studies demonstrated that at steady-state CD4RORγtIL-17 T-cell subsets and CD4Foxp3 cTreg supported tumorigenesis, whereas CD8 cytotoxic T-lymphocytes impeded tumor progression following IL-10 therapy. Suppression of tumor growth by CD8 T-cells was associated with enhanced tumor infiltration and cytotoxic granule exocytosis. These findings establish the utility of oral IL-10 as a potential new therapeutic in the management of colon cancer and shed light on the cellular mechanisms that underlie its antitumor activity.