Therapeutic Effects of Resiniferatoxin Related with Immunological Responses for Intestinal Inflammation in Trichinellosis

Abstract

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.

Resiniferatoxin promotes adult worm expulsion in Trichinella spiralis‐infected rats by Th2 immune response modulation

“…The expulsion of T spiralis is associated with the intestinal inflammatory response, regulated by thymus‐dependent immune responses and is characterized by a marked cellular infiltration in the mucosa and physical‐chemical changes in the intestinal environment, 7 which makes the hostile habitat for the parasite, thus facilitating its expulsion 10 . Although infected hosts initially mount a Th1‐type immune response, 11 T spiralis has the ability to polarize the immune response to a strong Th‐type 2 (Th2) cell response, protective and responsible for the parasite expulsion 12−14 . This Th2 immune response is characterized by the synthesis and release of cytokines, such as interleukin (IL)‐4, IL‐5 and IL‐13, which stimulate the synthesis of immunoglobulin (Ig)‐E, together with the production and activation of mast cells and eosinophils, promoting the T spiralis expulsion of the intestine 15,16 …”

Cytokine Profiling Plays a Crucial Role in Activating Immune System to Clear Infectious Pathogens

“…However, mast cells and eosinophils are involved in tissue damage, thus promoting the inflammatory response. It suggests that the protective role of the Th2 type immune response is not sufficient facing the challenge against helminth parasite infections, as it contributes to the development of immunopathology [178] (Figure 5).…”

Current Aspects in Trichinellosis

“…Pharmacotherapy used in Trichinellosis includes the use of antiparasitic and steroidal antiinflammatory drugs [114]. Currently, the antiparasitic treatment used for Trichinellosis is the administration of benzimidazoles, mainly albendazole and mebendazole, which are effective against the parasite [40,115].…”