Induction of Cytokine Transcripts in the Central Nervous System and Pituitary Following Peripheral Administration

FERNANDO J PITOSSI; ADRIANA DEL REY; ALEXA KABIERSCH; HUGO BESEDOVSKY

JOURNAL OF NEUROSCIENCE RESEARCH

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 1997 vol. 48 p. 287 - 298

0360-4012

The regionaldistribution and inducibility of cytokines in the normal brain is still a matter of controversy. As an attempt to clarify this issue, we studied the constitu- tive and induced expression of interleukin (IL)-1b, IL-6, tumor necrosis factor (TNF)-a,  andinterferon (IFN)-g mRNAs in the brain, pituitary, and spleen of mice using qualitative and semiquantitative reverse- transcription polymerase chain reaction. The contribu- tion of nonbrain cells to the cytokine transcripts detected was considered. With the exception of IFN-g mRNA, transcripts for the othercytokines were found to be constitutively present in the brain. Following i.p. injection of lipopolysaccharide (LPS) at a dose below those described to disrupt the blood-brain barrier (BBB), cytokinemRNA expressionwas increased in the spleen, the pituitary, and the brain. In the brain, the onset of transcription varied from 45 min (IL-1b, TNF-a) to 4 hr (IFN-g), and the peak of mRNA accumulation was observed at different times depend- ing on the cytokineand the brain region studied.IL-1 and IL-6 were highly expressed inthe hypothalamus and hippocampus, while TNF-a expression was more markedin the thalamus-striatum. The cortexwas the region in which cytokines were less inducible. The inducible expression ofcytokine mRNAs in the brain wasparalleled by stimulation of the hypothalamus- pituitary-adrenal axis. These results show the capacity of brain cells to synthesize different cytokine mRNAs in vivo and define thekinetics of their expression in several brain areas and in the peripheryin parallel to the activation of a neuroendocrinepathway by endotoxin