Reduced levels of transforming growth factor-beta1, interleukin-12 and increased migration inhibitory factor are associated with severe malaria

Abstract

In the present study, we investigated plasma levels of interleukin (IL)-12 and transforming growth factor (TGF-beta1) in malaria patients as these two cytokines regulate the balance between pro- and anti-inflammatory cytokines. We compared plasma IL-12 and TGF-beta1 levels in groups of malaria patients categorized as uncomplicated, severe, cerebral and placental malaria. Both TGF-beta1 and IL-12 levels were significantly reduced in peripheral plasma of adults with severe and cerebral malaria as well as in plasma of Tanzanian children with cerebral malaria (P<0.05). Similar results were observed with both placental and peripheral plasma of pregnant women who were infected with Plasmodium falciparum. IL-18, a cytokine known to be critical for the induction of IFN-gamma along with IL-1, was produced more in uncomplicated adult patients than in aparasitimic healthy controls (P<0.05). However, IL-18 response rate declined as the symptoms of the disease became more severe suggesting that the IL-18 response may be impaired with increased malaria severity. Together, the results of the three cytokines support the notion that imbalance between pro- and anti-inflammatory cytokines may contribute to the development of severe malaria infection. With malaria infection during pregnancy, we demonstrated that macrophage migration inhibitory factor (MIF) levels in infected placental plasma were significantly higher than those in the paired peripheral plasma (P<0.05). MIF, therefore, may play an important role in the local immune response to placental P. falciparum infection.