Impact of Albendazole on Cytokine and Chemokine Response Profiles in Echinococcus multilocularis-Inoculated Mice

Abstract

Objective. Alveolar echinococcosis (AE) is a zoonosis caused by the larval stage of the metacestode Echinococcosis multilocularis with a tumor-like behavior in the targeted organ, especially in the liver. Surgery with albendazole is first-line modality for AE. Drug discontinuation is usually based upon the parasitic viability shown by the positron emission tomography (PET) scan. However, as a demanding and expensive method, it is not widely practiced in majority of the endemic regions. Further understanding on the cytokine and chemokine response profiles in AE patients may provide an interesting insight for potential markers in viability assessment. Methods. Mice were inoculated with Echinococcus multilocularis intrahepatically to develop the hepatic AE murine model. Oral albendazole administration was then applied for three months after the first inoculation, and peripheral and regional immune cells including type 1 T helper cells (Th), Th2, Th17, regulatory T (Treg) cells, related cytokines, and chemokines were examined. Results. The hepatic AE lesion was confirmed by ultrasound examination resulting in a successful rate of 70%. Among the 17 cytokines and chemokines detected, plasma levels of IL-23 were significantly higher in E. multilocularis-infected mice when compared to the control group; furthermore, more obvious increasing levels were found after albendazole treatment ( p < 0.05 ). All chemokine levels other than eotaxin and MCP-3 were slightly higher in E. multilocularis-infected mice compared to the control group ( p > 0.05 ). Eotaxin levels were significantly decreased in mice with E. multilocularis infection followed by albendazole treatment ( p < 0.05 ). Both IL-17A and IL-23 expressions in hepatic AE lesions were significantly higher and related with disease activity. Conclusion. Albendazole administration influenced the balance of immune response and promotes the secretion of proinflammatory factors which is beneficial to parasite clearance. IL-23 seems to be associated with the successful albendazole treatment in mice with E. multilocularis infection; such a change could be translated into clinical application in the near future.

Appraisal of Chitosan-Coated Lipid Nano-Combination with Miltefosine and Albendazole in the Treatment of Murine Trichinellosis: Experimental Study with Evaluation of Immunological and Immunohistochemical Parameters

“…Treatment with ABZ caused a significant reduction in GATA3 and a non-significant reduction in GPX1 expression, which agreed to some extent with results documented by Wu et al [ 48 ] and Kim et al [ 58 ], where ABZ showed a non-significant reduction of messenger ribonucleic acid (mRNA) expressions of GATA3 transcription factor and the mRNA expression of the antioxidant enzymes catalase, GPX1, and GPX3 used in the treatment of experimental Echinococcus multilocularis and prostate cancer, respectively. This difference might be due to different drug regimens and infections.…”

“…All treated groups in the present study showed a significant reduction in the level of IL-12 in comparison to the positive control group either in intestinal or muscular phases, which coincides with Abd El-Hamed et al [46], and Salama et al [47] results, where a significant reduction in serum TNF-was observed in all treated groups either with ABZ or herbal extracts at different PI periods. However, the significant reduction that occurred with ABZ either alone or loaded with NLCS did not concede with Wu et al [48], where ABZ caused a non-significant reduction of the plasma level of IL-12 (p > 0.05) in Echinococcus multilocularisinfected mice. Also, the significant reduction that occurred with MFS either alone or combined with NLCs did not concede with Palić et al [49,50], who stated that MFS in the treatment of Leishmania targeted the Th-1 signaling, increasing the concentrations of pro-inflammatory Th-1 cytokines, such as IFN-γ and IL-12 and induced a shift of the macrophage phenotype, which is essential for the clearance of intracellular pathogens which we refer to the use of different infection models.…”

Indoleamine 2,3-dioxygenase 1 signaling orchestrates immune tolerance in Echinococcus multilocularis-infected mice

“…It has been reported that E. multilocularis infection prevents the maturation of DCs, as illustrated by the diminished expression of various costimulatory molecules and chemokine receptors (10,41). To investigate whether IDO1 is involved in the maturation of DCs in mice infected with E. multilocularis, we next evaluated its effects on the expression of multiple phenotypic maturation markers, namely CD80, CD86, MHC II, CD11b, CXCR4, and CCR7, on DCs in infected IDO1 -/and WT mice (Figure 3A).…”

Characterization of protein cargo of Echinococcus granulosus extracellular vesicles in drug response and its influence on immune response

“…However, in the present study, antigen 5 shows a similar abundance in all studied conditions, indicating that the higher ratio observed in albendazole-treated patients probably corresponds to an increase in cyst permeability rather than greater antigen production and release in either a soluble or sEV-linked manner. As we mentioned before, the increase in cyst permeability by albendazole favors the leakage of antigens that promote antibody production [ 69 ] and the pro-inflammatory response, which is beneficial for limiting parasitic progression in both CE and alveolar echinococcosis [ 25 , 70 , 71 ].…”