Immunomodulatory and anti-inflammatory effects of fluvoxamine during the intestinal phase of Trichinella spiralis infection in mice

Trichinellosis is a meat-borne zoonosis of ubiquitous distribution. The severity is variable, and fatalities may occur. Immune-mediated inflammation plays an important role in the pathogenesis of the disease. Thus, safe and effective compounds with anti-inflammatory properties are needed. Our study was designed to evaluate the effects of fluvoxamine as an adjuvant to albendazole during the intestinal and migratory phases of trichinellosis. Therefore, Trichinella spiralis-infected mice were treated with either fluvoxamine, albendazole, or a combination of both drugs. Notably, the parasite burden was reduced in the intestines and muscles of fluvoxamine-treated mice compared to the infected control, denoting a detrimental effect of the drug against Trichinella spiralis. Moreover, in comparison with the infected control, there was a marked improvement in intestinal and muscle inflammation with the treatment, evidenced by the reduction in COX-2 and TNF-α and the decrement of inflammatory infiltrates in tissues. The expression of iNOS was also reduced in the muscles. Treatment with fluvoxamine alleviated the oxidative stress in the intestines and muscles with a reduction in malondialdehyde and H₂O₂ and an increase in reduced glutathione levels. Finally, fluvoxamine moderated the immune response, as evidenced by the downregulation of the levels of IL-4 and IFN-γ and the increase of those of IL-10 in tissues. Characteristically, all these beneficial effects were maximal in mice receiving the combined treatment. In conclusion, fluvoxamine administration during the early phase of trichinellosis exhibited immunomodulatory and anti-inflammatory activities that potentiated the efficacy of albendazole. Therefore, fluvoxamine could be considered a useful adjuvant treatment in trichinellosis.