resiniferatoxin and 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.

Topics: Animals; CD4-Positive T-Lymphocytes; Cytokines; Diterpenes; Eosinophils; Humans; Inflammation Mediators; Intestinal Diseases, Parasitic; Intestines; Leukocyte Count; Th1 Cells; Th2 Cells; Trichinella spiralis; Trichinellosis

The immune response during T spiralis infection is characterized by an increase in eosinophils and mast cells, as well as Th2 cytokine production, such as interleukin (IL)-4, IL-10 and IL-13, promoting T spiralis expulsion from the host. However, this response damages the host, favouring the parasite survival. In the search for new pharmacological strategies that protect against T spiralis infection, a recent study showed that treatment with resiniferatoxin (RTX) modulates the Th1 cytokines production, reducing muscle parasite burden.. To evaluate the effect of RTX treatment on the Th2 cytokines production, the number of eosinophils, mast cells and the intestinal expulsion of T spiralis.. Serum levels of IL-4, IL-10 and IL-13 were quantified by ELISA; the number of eosinophils, mast cells and the adult worms of T spiralis in the small intestine was quantified.. RTX treatment increased serum levels of IL-4, IL-10 and IL-13, and it decreases intestinal eosinophilia, however, favours the mastocytosis, promoting T spiralis intestinal expulsion.. These findings suggest that RTX is capable to modulate the Th2 immune response, promoting T spiralis expulsion, which contributes to the defence against T spiralis infection, placing the RTX as a potential immunomodulatory drug.

Topics: Animals; Cytokines; Diterpenes; Immunity; Rats; Th2 Cells; Trichinella spiralis; Trichinellosis

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.

Topics: Animals; Cytokines; Diterpenes; Female; Helminthiasis; Intestinal Diseases, Parasitic; Intestines; Mice; Mice, Inbred BALB C; Muscles; Rats; Th1 Cells; Trichinella spiralis; Trichinellosis; Tumor Necrosis Factor-alpha

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

Topics: Animals; Antinematodal Agents; Dinoprostone; Diterpenes; Eosinophils; Female; Inflammation Mediators; Intestines; Leukocyte Count; Rats; Rats, Sprague-Dawley; Trichinella spiralis; Trichinellosis; Tumor Necrosis Factor-alpha