A first step has been taken toward a treatment for gonorrhea, a sexually transmitted disease (STD) notorious for its high reinfection rates. This news comes within days of a troubling update from the U.S. Centers for Disease Control that placed the STD on a list of “urgent threats” in the fight against drug-resistant bacteria. According to the CDC, Neisseria gonorrhoeae, the bacteria that causes the malady in humans—which can initially result in painful inflammation and discharge, and can cause infertility and even death if not treated—requires urgent and aggressive action from the medical research community. Researchers from the University at Buffalo, S.U.N.Y., think the answer may lie in marshaling the immune system against gonorrhea.
The study, published in The Journal of Infections Diseases, found gonococcal infections in mice could be cured by introducing into the genital tract a cytokine, or immunoregulatory protein, known asinterleukin-12 (IL-12), which is also being investigated as a cancer-fighting agent. Michael Russell, a microbiologist and immunologist at S.U.N.Y. Buffalo and one of the study’s authors, says that his 20-year investigation into gonorrhea and its resilience led him to suspect that it was actively altering immune systems, preventing human hosts from developing long-term resistance to it.
The exact mechanism of the alteration remains unclear, but Russell thinks it has to do with the two distinct “arms” of vertebrate immune systems: innate and adaptive. Russell observed high levels of a cytokine called interleukin-10 (IL-10) in gonococcal infections, and observed that it induces an innate immune response. IL-10 seems to suppress adaptive responses—like the formation of antibodies that can be used again to fight later infections—in favor of more general, short-term innate responses. Meanwhile, the innate responses, such as inflammation, are easy for N. gonorrhoeaeto beat. If IL-12 could counteract the effects of IL-10, Russell hypothesized, it could help the body fight gonorrhea more effectively, and could be used in a treatment for the STD. When his colleague Nejat Egilmez developed a new delivery mechanism for the otherwise toxic IL-12, in which microspheres of slow-releasing nanoparticles of the cytokine could be targeted directly onto immunosuppressant tumors, Russell’s team decided to try injecting them into the vaginal tracts of infected mice.
“And it worked,” he says, “very nicely.” Not only did mice treated with IL-12 respond more quickly to antibiotics, they were also significantly less likely to be reinfected than controls when exposed to the same strain a month later. “We found that the IL-12 treatment allows the development of an adaptive immune response not usually seen,” Russell says. It seems that by counteracting the IL-10 present at gonococcal infections, the treatment prevents immune systems from being tricked out of developing adaptive responses to the disease. The effect, he says, lasts for several months.