Tamoxifen Suppresses the Immune Response to Plasmodium berghei ANKA and Exacerbates Symptomatology

Abstract

Malaria is the most lethal parasitic disease in the world. Mortality and severity in symptoms are higher in men than women, suggesting that oestrogens, which are in higher concentration in females than in males, may regulate the immune response against malaria. Tamoxifen, a selective oestrogen receptor modulator used in breast cancer treatment due to its antagonistic effect on oestrogen receptors α and β, is also studied because of its potential therapeutic use for several parasitic diseases. However, most studies, including one in malaria, have not addressed the immunomodulatory role of tamoxifen. In this work, we evaluated the effect of tamoxifen on the immune response of CBA/Ca mice against Plasmodium berghei ANKA. This study showed for the first time that tamoxifen increased parasite load, aggravated symptoms by decreasing body temperature and body weight, and worsened anaemia. Additionally, tamoxifen significantly increased the splenic index and the percentages of CD4+ and NK+ cells on day eight post-infection. By contrast, tamoxifen decreased both CD8+ and B220+ populations in the spleen and decreased the serum levels of IL-2, IL-6, and IL-17. Our findings support the notion that tamoxifen is a potent immunomodulator in malaria-infected mice and suggest caution when administering it to malaria-infected women with breast cancer.

Tamoxifen Increased Parasite Burden and Induced a Series of Histopathological and Immunohistochemical Changes During Chronic Toxoplasmosis in Experimentally Infected Mice

“…The present findings are in harmony with those reported elsewhere ( Chen et al, 2019 ). This effect could be driven by the immunomodulatory effect of tamoxifen which was also reported in a other parasites ( Cervantes-Candelas et al, 2021 ). Given the above information, the molecular results confirmed the findings obtained by parasitological, histopathological, immunohistochemical methods.…”

“…In the same work, there was observed a significant increase in IgM and IgG titers of the parasite in groups treated with tamoxifen for 4 weeks, which is consistent with the present findings. Similarly but in other parasites, a previous study reported that tamoxifen increased parasite load during the infection by Plasmodium berghei and exacerbated the symptoms of infected animals combined with suppression of the immune response ( Cervantes-Candelas et al, 2021 ). The possible explanation for this effect could be attributed to the immunomodulatory role of tamoxifen and the potential involvement of different cellular compartments of the immune system which was reported in other parasites ( Cervantes-Candelas et al, 2021 ).…”

Antimalarial evaluation of tamoxifen: a study in parasitized mice

“…30 TMX exhibited no curative and suppressive antiplasmodial activities in this study. Similarly, Cervantes-Candelas et al, 13 reported that TMX had no antiplasmodial effect on CQ resistant P. berghei-infected mice. Staines et al, 11 also showed that TMX had no antiplasmodial effect on P. falciparum while Sing et al, 12 reported no antiplasmodial effect on P. yoelii nigeriensisinfected mice.…”

“…Studies showed it had no antiplasmodial effects on P. falciparum growth, 11 Plasmodium yoelii nigeriensis-infected mice 12 and chloroquine (CQ) resistant Plasmodium berghei-infected mice. 13 But some studies documented in-vitro and in-vivo antiplaspmodial activities of TMX on Plasmodium falciparum and Plasmodium berghei (ANKA), respectively. 14 Thus it is imperative that further studies are performed to ascertain the antiplasmodial activity of TMX.…”

Advances in the Immunobiology of Parasitic Diseases

“…Another study dealing with the role of sex hormones on susceptibility to protozoan parasites is presented by Cervantes-Candelas et al [ 4 ], who examined the role of tamoxifen in malaria. This team point out that malaria is the most lethal parasitic disease in the world.…”