The Neurosteroid Analog LMM102 Enhances Host Resistance to T. solium Infection

Abstract

Carriers of the tapeworm Taenia solium are the main risk factor in the transmission of both human neurocysticercosis and porcine cysticercosis. One quarter of the world’s human population is exposed to intestinal helminthic parasites; consequently, agents that can eliminate and/or reduce the incidence of carriers could significantly enhance human and animal health. Neurosteroid hormones up regulate host resistance to infections by viruses, bacteria and parasites. An analogue (LMM102) devoid of androgenic or estrogenic activity was tested in vitro and in vivo for its ability to modulate T. solium reproduction, growth, viability, and infectivity. Three groups of female adult hamsters (Mesocricetus auratus) were tested; the first were injected subcutaneously (SC) with 2 mg/kg of LMM102, while the other two served as vehicles and untreated control groups, respectively. After two weeks, all animals were orally infected with 4 viable T. solium cysticerci. At 2 weeks post infection, LMM102 -treated hamsters showed an 80% reduction in adult worm recovery with a 75% reduced length as compared to either vehicle or untreated infected controls. Only in LMM102 treated, infected animals, spleen and mesenteric lymph nodes were increased with 5-fold elevation of leukocyte proliferation. Duodenal mucosa cytokine IL-4, IL-6 and TNFwere also elevated. These results show that LMM102 protects hamsters from T. solium adult tapeworm establishment by improving intestinal mucosal immunity, suggesting the potential use of this hormone analogue as novel enhancer of the gut immune response against intestinal helminthic infections and other gastrointestinal tract-related disorders.