Expression of proinflammatory cytokines in four regions of the brain in Macaque mulatta (rhesus) monkeys infected with Plasmodium coatneyi

We have characterized brain cytokine expression profiles in the Plasmodium coatneyi/rhesus (Macaque mulatta) malaria model. Eight rhesus monkeys were included in the study; four were infected with P. coatneyi, and four were u sed as uninfected controls. All inoculated animals became infected. Eleven days after parasite inoculation, the rhesus monkeys were killed and tissue samples from 4 regions of the brain (cortex and white matter of the cerebru m, cerebellum, and midbrain) were collected for quantitation of mRNA expres sion of cytokines, adhesion molecules, and inducible nitric oxide synthetas e (iNOS) by reverse transcriptase-polymerase chain reaction (RT-PCR). The e xpression levels of tumor necrosis actor-alpha (TNF-alpha), gamma interfero n (IFN-gamma), interleukin-l-beta (IL-1 beta), intercellular adhesion molec ule-1 (ICAM-1) and inducible nitric oxide synethetase (iNOS) were highest i n the cerebellum of infected animals, correlating well with pathologic obse rvations of sequestration of parasitized erythrocytes in this region of the brain. Infected animals also had higher TNF-alpha expression levels in the cortex and IL-1 beta expression levels in the cortex, white matter, and mi dbrain. Thus, the expression of pro-inflammatory and T helper-1 (TH-1) cyto kines, adhesion molecules, and iNOS appears to predominate in the cerebellu m of infected rhesus monkeys.