Thalidomide influences the function of macrophages and increases the survival of Plasmodium berghei-infected CBA mice

Malaria remains a major cause of morbidity and mortality in vast areas of the world, mainly due to the severe forms of Plasmodium falciparum infection. The exacerbated immune response, with increased production of TNF and reactive nitrogen and oxygen intermediates, plays a role in the complex pathogenesis of the disease. It is recognised that thalidomide decreases TNF production and may modulate several functions of the immune system. This work evaluated the influence of thalidomide on macrophage functions, and its ability to protect against severe disease. Plasmodium berghei ANKA-infected mice were (n = 11) or were not (n = 10) intra-gastric treated with thalidomide (150 mg/kg per day), and two other control groups not infected with the parasite were (n = 8) or were not (n = 10) treated with the drug, and macrophage production of hydrogen peroxide and nitric oxide, and phagocytosis were assessed on the eighth day post-infection. Thalidomide increased the survival time of infected mice, in parallel with a 26.5% increase of the mean of macrophage phagocytic index, and augmented in 13% the mean of the production of hydrogen peroxide and in 45% the mean of nitric oxide production by macrophages related to the non-treated P. berghei-infected mice. Our data indicate that thalidomide improves the outcome of P. berghei ANKA-infected CBA mice and suggest that this drug could represent a new alternative to be associated to antimalarial drugs to decrease the morbidity and mortality of severe malaria in non-pregnant individuals