الفهرس 
Diethylcarbamazine Citrate and its immunomodulatory role.Only 14 pages are availabe for public view
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Abstract
Filariasis is a parasitic disease caused by an infection with filarial worms. Despite various strategies to develop drugs, still an estimated 200 million people remain infected by filarial nematodes till now. So far, the existing anti-filarial drugs predominantly target microfilariae and remain ineffective towards the adult filarial parasites and their excretory- secretory products (ES). We studied the effect of female ES of the filarial worm Setaria equina and the drug Diethylcarbamazine citrate (DEC) and their combination on the murine production of Interferon- gamma (IFN-γ) and Interleukin- 10 (IL-10). Seventy male Swiss mice, (22 ± 2 g) of about 4-6 weeks old were used and divided into seven groups each one consisted of 10 male mice as following: 1st control (1 ml of Tyrode’s solution), 2nd (0.25 ml ES) , 3rd (1 ml ES), 4th ( 25 mg/kg DEC in 0.25 ml Tyrode’s), 5th ( 100 mg/kg DEC in 1 ml Tyrode’s) , 6th (25 mg/kg DEC in 0.25 ml ES) and 7th (100 mg/kg DEC in 1 ml ES). These doses were given to all groups at days 0, 14, 28 and 42. ES was tested using both ex vivo (release of cytokines from splenocytes) and in vivo (serum cytokine levels) assays for induced production of IFN-γ and IL-10. For ex vivo assays, both 0.25 ml and 1 ml of ES groups could induce the highest level of IFN-γ release compared to the control group (P< 0.001). In contrast, the same mice groups showed the highest decrease in IL-10 levels (P< 0.001). Although ES showed significant (P< 0.001) effects with DEC mice groups, its effect on (ES + DEC) did not show synergistic effects. For in vivo tests, serum levels of IFN-γ were the highest, while IL-10 levels were the lowest in ES mice groups (P< 0.001). Similarly, DEC groups showed significant effects for the increase and decrease in IFN-γ and IL-10 levels, respectively, while (ES + DEC) groups did not show synergistic effects. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect secreted IL-15 transcripts in liver. Immunoblotting has shown a higher expression of IL-15 in ES mice groups with observably higher expression in groups received 1 ml ES than 0.25 ml ES (P< 0.001). IL-15 protein was localized using immunohistochemistry where the staining pattern in liver suggested that tissue resident Kupffer cells were the main producers and they were present in abundance in mice receiving high dose of ES. This study could demonstrate that the repeated doses of female S. equina ES could increase the production of IFN-γ significantly. Also, ES- immunized groups showed higher expression of IL-15. The significant increase in IFN- γ and IL-15 in mice immunized with ES suggested a design for a new vaccine technique that will be protective against intracellular pathogens.