Resiniferatoxin lowers TNF‐α, NO and PGE₂ in the intestinal phase and the parasite burden in the muscular phase of Trichinella spiralis infection

Abstract

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.

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

“…However, no significant difference was observed in the helminth parasite expulsion, although iNOS knockout mice showed a decrease in intestinal pathology compared to wild-type animals. These results suggest that NO is not required for the helminth parasite expulsion, but its production is responsible for the intestinal pathology [155,168]. With respect to IL-1β, it is well known that it participates in the intestinal inflammatory response in the helminth parasites infection, observing high levels during intestinal infection.…”

“…PAMPs derived from helminth parasites induce the activation and maturation of dendritic cells [147,148], promoting the development of the Th1 immune response [149], which results in a significant increase of Th1 cytokines such as IL-12 [150][151][152], INF-γ [149][150][151][152][153], IL-1β [152,154], and TNF-α [150][151][152]155] (Figure 5). However, in recent years, several studies have shown that this immune response of Th1 type favors infection by helminth parasites.…”

“…Studies have shown that TNF-α is a cytokine that is produced during intestinal infection by helminth parasites [150,151,159], which is necessary in the protection against the parasite through the Th2 immune response [160]. However, several studies have associated the production of TNF-α with the development of intestinal pathology during infection by helminth parasites [155,161,162]. One of the effects of TNF-α is the iNOS expression and consequently the NO production [163][164][165].…”

Current Aspects in Trichinellosis

“…The Th1 type immune response against T. spiralis is characterized by a significant increase in Th1 cytokines such as IL-12 [67][68][69], INF-γ [48,[67][68][69][70], IL-1β [69,71] and TNF-α ( Figure 4) [ [67][68][69]72]. In recent years, studies have shown that the production of Th1 cytokines is directly associated with the development of the inflammatory response and intestinal pathology, which favors the infection by T. spiralis.…”

Adipose Tissue and Inflammation

“…Although TNF-α, a potent pro-inflammatory cytokine [9,10] was the first cytokine discovered that is secreted by adipose tissue [11], the leptin was the first molecule with hormonal activity that is secreted by adipocytes. Since then, multiple molecules called adipokines have been discovered as factors that are secreted by adipocytes or by the stromal-vascular fraction, composed mainly by macrophages, neutrophils, lymphocytes, fibroblast, and endothelial cells.…”