PRODUCT ION OF THE CYTOKINES INTERLEUKIN-1 AND INTERLEUKIN-6 BY MURINE BRAIN MICROVESSEL ENDOTHELIUM AND SMOOTH-MUSCLE PERICYTES

Murine brain microvessel endothelial cells and smooth muscle/pericytes (SM/P) cells were cultured from newborn BALB/c (normal strain) and SJ L/j (autoimmune-prone strain) mice. These cells were evaluated for the ir ability to produce interleukin (IL)-1 and IL-6 cytokines. The expre ssion of mRNA for IL-1 and IL-6 was shown in highly purified BALB/c en dothelial cells and SM/P cells using polymerase chain reaction with sp ecific primers for IL-1alpha, IL-1beta and IL-6. IL-6 but not IL-1 mRN A was detected in unstimulated SJL/j brain microvessel cells. The pres ence of IL-1 and IL-6 mRNA in the BALB/c brain microvessel endothelial cells and SM/P was confirmed by in situ hybridization. By DIO.G4.1 as say, unstimulated BALB/c endothelial cells were shown to produce activ e IL-1 to a higher degree than SM/P. By B9 bioassay, a low amount of a ctive IL-6 was detected in the supernatant of endothelial cells and SM /P. The production of IL-1 and IL-6 in the bioassays was upregulated b y lipopolysaccharide (LPS) activation of the cells in a time- and dose -dependent way. IL-6 production was also shown to be upregulated by IL -1beta activation of the cells. Brain microvessel endothelial cells of SJL/j origin released equivalent amounts of IL-6 compared to endothel ial cells of BALB/c origin. However, the production of IL-6 was marked ly higher in SM/P of SJL/j origin than in those of BALB/c origin. Thes e observations, together with our previous data showing that brain mic rovessel SM/P cells produce GM-CSF, emphasize the possibility for acti ve participation of brain microvasculature SM/P as well as endothelium in inflammatory reactions of the central nervous system.