Involvement of interleukin-1 beta in the mechanism of human immunodeficiency virus type 1 (HIV-1) recombinant protein gp120-induced apoptosis in the neocortex of rat

The effect of subchronic intracerebroventricular injection of the human imm unodeficiency virus type 1 (HIV-1) recombinant protein gp120 (100 ng, given daily for up to seven consecutive days) on interieukin-1 beta expression w as studied by immunohistochemistry in the brain of adult rats. In compariso n to control, bovine serum albumin (300 ng, given intracerebroventricularly for up to seven days) -treated animals (n=6), interreukin-1 beta immunorea ctivity increased in the brain cortex and hippocampus of rats (n=6) receivi ng a single injection of the viral protein 24 h before analysis with more s ubstantial increases being observed in these regions of the brain (n=6) aft er seven days treatment. Double-labelling immunofluorescence experiments su pport a neuronal and, possibly, a microglial cell origin for gp120-enhanced interleukin-1 beta expression. Transmission electron microscopy analysis o f brain tissue sections revealed that combination treatments (given intrace rebroventricularly daily for seven days) with gp120 (100 ng) and interleuki n-1 receptor antagonist (80 ng) or with the interleukin converting enzyme i nhibitor II (100 pmol), but not with leupeptin (100 pmol), prevented apopto tic death of rat (n=6/group) brain cortical cells typically elicited by the viral protein. These data demonstrate that gp120 enhances interleukin-lp e xpression in the brain and this may be involved in the mechanism underlying apoptosis induced by gp120 in the brain cortex of rat. Further support to this hypothesis comes from the evidence that intracerebroventricular inject ion of murine recombinant interleukin-1 beta (200 U, given daily for seven consecutive days) produces DNA fragmentation in the brain cortex of rat (n= 6). Interestingly, the latter treatment enhanced nerve growth factor level in the hippocampus but not in the cerebral cortex and this coincides with a similar effect recently reported in identical brain areas of rats treated likewise with gp120. In conclusion, the present data demonstrate that treatment with gp120 enhan ces interleukin-1 beta expression and this participates in the mechanism of apoptotic cell death in the brain cortex of rat. By contrast, in the hippo campus, gp120-enhanced interreukin-1 beta expression elevates nerve growth factor that may prevent or delay apoptosis in this plastic region of the ra t brain. (C) 1999 IBRO. Published by Elsevier Science Ltd.