Interactions between HIV-infected monocyte-derived endothelial cells result in increased expression of CC chemokines

The presence of perivascular monocytic in®ltration is a major hallmark of HIV1-associated dementia. Since CC chemokines are chemoattractant cytokines that are able to attract T cells and monocytes/macrophages to sites of in ̄ammation, and since in®ltrating monocytes/macrophages remain in close contact with the brain endothelium, we investigated whether interactions between HIV-1-infected macrophages and brain endothelium result in an altered chemokine production. We found an increased mRNA expression of monocyte chemotactic protein-1 (MCP-1), macrophage in ̄ammatory protein (MIP) -1a and MIP-1b, and RANTES by macrophages after HIV-1 infection. Interactions between HIV-infected macrophages and brain microvascular endothelial cells resulted in an additional upregulation of chemokine mRNA expression, during cell ± cell contact as well as in a trans-well system. Since IL1b can function as a modulator of chemokine expression we investigated if interleukin-1b could be involved in the regulation of chemokine induction. Coculturing of HIV-infected macrophages and endothelial cells resulted in immune-activation as indicated by increased mRNA expression of IL-1b. Subsequently, addition of a neutralizing antibody against IL-1b resulted in altered chemokine expression by macrophages, but not by endothelial cells. Thus, IL-1b appears to play a major role in the regulation of chemokines during cellular interactions in HIV-associated dementia, but other factors may also be involved. Journal of NeuroVirology (2000) 6, 382 ± 389.