Cytokine expression in the brain in human cerebral malaria.
Evidence from clinical studies and murine models supports a role for cytokines in the pathogenesis of human cerebral malaria (CM). In this study, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to investigate expression of mRNA for transforming growth factor (TGF)-beta, interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha in human postmortem tissue. Immunohistochemistry was used to examine the distribution of cytokine protein. TGF-beta was expressed in normal brain, in CM, and in meningitis and encephalitis. IL-1beta was absent from normal brain but was detected in CM and other cerebral infections. TNF-alpha mRNA was expressed only in CM, although TNF-alpha protein was also seen in meningitis. Cytokine mRNA expression in the brain did not correlate with the density of parasitized erythrocytes detected using RT-PCR for major surface protein-2. This report of RT-PCR on postmortem human tissues infected with CM demonstrates induction of the proinflammatory cytokines TNF-alpha and IL-1beta in the brain.
Brown
H
H
Nuffield Department of Clinical Biochemistry, Oxford-Wellcome Centre for Tropical Medicine, John Radcliffe Hospital, Headington, United Kingdom.
Turner
G
G
Rogerson
S
S
Tembo
M
M
Mwenechanya
J
J
Molyneux
M
M
Taylor
T
T
D000953:Antigens, Protozoan / Q000096:biosynthesis / Q000235:genetics; D001921:Brain / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D016779:Malaria, Cerebral / Q000378:metabolism*; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D000953:Antigens, Protozoan; D007375:Interleukin-1; D015800:Protozoan Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C065974:merozoite surface protein 2, Plasmodium