During the course of infection with Trichinella spiralis, an inflammatory response is triggered at the intestinal level in the host, playing a crucial role in the expulsion and elimination of the parasite. However, several studies have demonstrated that this inflammatory response is harmful to the host; hence, the importance of studying molecules with therapeutic potential like resiniferatoxin, which is known to have an anti-inflammatory effect both in vitro and in vivo. In this article, we evaluated the anti-inflammatory activity of resiniferatoxin during the intestinal phase of T. spiralis infection by quantitatively determining the levels of TNF-α, NO and PGE as well as the percentage of eosinophils in the blood and intestinal pathology. In addition, parasite burden was determined during the muscle infection. Our results show that resiniferatoxin lowered the serum levels of TNF-α, NO and PGE , as well as the percentage of eosinophils in the blood and intestinal pathology during the intestinal infection. Moreover, resiniferatoxin also lowered the parasite burden in muscle, resulting in a reduction of the humoral response (IgG) associated to treatment with resiniferatoxin. These findings suggest a potential therapeutic use of the anti-inflammatory effect of resiniferatoxin, which also contributes to host defence against the challenge of T. spiralis infection.

In the early stage of the intestinal phase of Trichinella spiralis infection, the host triggers a Th1-type immune response with the aim of eliminating the parasite. However, this response damages the host which favours the survival of the parasite. In the search for novel pharmacological strategies that inhibit the Th1 immune response and assist the host against T. spiralis infection, a recent study showed that resiniferatoxin had anti-inflammatory activity contributed to the host in T. spiralis infection. In this study, we evaluated whether RTX modulates the host immune response through the inhibition of Th1 cytokines in the intestinal phase. In addition, it was determined whether the treatment with RTX affects the infectivity of T. spiralis-L1 and the development of the T. spiralis life cycle. Our results show that RTX decreased serum levels of IL-12, INF-γ, IL-1β, TNF-α and parasite burden on muscle tissue. It was observed that T. spiralis-L1 treated with RTX decreased their infectivity affecting the development of the T. spiralis life cycle in mouse. These results demonstrate that RTX is able to inhibit the production of Th1 cytokines, contributing to the defence against T. spiralis, which places it as a potential drug modulator of the immune response.

Currently, it is estimated that more than 11 million humans in the world are infected by helminth parasites of Trichinella species, mainly by Trichinella spiralis (T. spiralis), responsible for causing Trichinellosis disease in both animals and humans. Trichinellosis is a cosmopolitan parasitic zoonotic disease, which has direct relevance to human and animal health, because it presents a constant and important challenge to the host's immune system, especially through the intestinal tract. Currently, there is an intense investigation of new strategies in pharmacotherapy and immunotherapy against infection by Trichinella spiralis. In this chapter, we will present the most current aspects of biology, epidemiology, immunology, clinicopathology, pharmacotherapy and immunotherapy in Trichinellosis.

The immune response against Trichinella spiralis at the intestinal level depends on the CD4+ T cells, which can both suppress or promote the inflammatory response through the synthesis of diverse cytokines. During the intestinal phase, the immune response is mixed (Th1/Th2) with the initial predominance of the Th1 response and the subsequent domination of Th2 response, which favor the development of intestinal pathology. In this context, the glucocorticoids (GC) are the pharmacotherapy for the intestinal inflammatory response in trichinellosis. However, its therapeutic use is limited, since studies have shown that treatment with GC suppresses the host immune system, favoring T. spiralis infection. In the search for novel pharmacological strategies that inhibit the Th1 immune response (proinflammatory) and assist the host against T. spiralis infection, recent studies showed that resiniferatoxin (RTX) had anti-inflammatory activity, which decreased the serum levels of IL-12, INF-γ, IL-1β, TNF-α, NO, and PGE2, as well the number of eosinophils in the blood, associated with decreased intestinal pathology and muscle parasite burden. These researches demonstrate that RTX is capable to inhibit the production of Th1 cytokines, contributing to the defense against T. spiralis infection, which places it as a new potential drug modulator of the immune response.

The cover image, by J. L. Muñoz‐Carrillo et al., is based on the Original Article Resiniferatoxin modulates the Th1 immune response and protects the host during intestinal nematode infection, DOI: .