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Estradiol, but Not Dehydroepiandrosterone, Decreases Parasitemia and Increases the Incidence of Cerebral Malaria and the Mortality in <i>Plasmodium berghei</i> ANKA-Infected CBA Mice

2006; Karger Publishers; Volume: 13; Issue: 1 Linguagem: Inglês

10.1159/000093271

1423-0216

Rosana Maria Feio Libonati, Maristela G Cunha, José Maria de Souza, Marcos V.N. Santos, Salma Gomes de Oliveira, Cláudio Tadeu Daniel‐Ribeiro, Leonardo J. M. Carvalho, José Luíz Martins do Nascimento,

Mosquito-borne diseases and control

<i>Objective:</i> The effect of castration and subsequent replacement of dehydroepiandrosterone (DHEA) or estradiol on parasitemia, mortality and incidence of cerebral malaria (CM) was evaluated in CBA mice infected with <i>Plasmodium berghei</i> ANKA. <i>Methods:</i> Female mice were castrated, and groups of 12–15 animals received daily injections of DHEA, estradiol or saline. Four days after the start of treatment, mice were inoculated with 1 × 10⁶<i>P. berghei</i> ANKA-parasitized erythrocytes. DHEA treatment was continued during the 5 days after infection, and estradiol was administered during the follow-up. Parasitemia was evaluated daily in Giemsa-stained blood smears. Signs of CM were determined by the manifestation of coma, limb paralysis and/or convulsions. Plasma TNF-α levels were evaluated by sandwich ELISA. Nitric oxide synthase (NOS) activity in the brain of moribund mice was measured by the method of Bredt and Snyder. <i>Results:</i> In non-castrated infected mice, the incidence of CM was 50%, and plasma TNF-α increased and brain NOS activity decreased compared to non-infected controls. Castration had no major effect on the parameters analyzed (parasitemia, mortality, CM incidence, TNF-α levels or NOS activity). Estradiol replacement caused a decrease in parasitemia but resulted in higher CM incidence and faster mortality, with an increase in NOS activity. <i>Conclusions:</i> Estradiol modulated the immune response of <i>P. berghei</i> ANKA-infected CBA mice, decreasing parasitemia and increasing NOS activity, and impacted negatively on survival and CM incidence, showing that neuroimmunoendocrine interactions are important in the physiopathogenesis of malaria infections.