IL-1 beta, IL-1 receptor type I and iNOS gene expression in rat brain vasculature and perivascular areas

The mechanism by which IL-1 beta exerts its actions in the brain during systemic inflammation is not fully understood, as neither IL-1 receptor gene expression nor IL-1 binding have been identified in significant levels in key areas that respond to IL-1 beta. Having hypothesized that perivascular nitric oxide (NO) might modulate the effects of systemic IL-1 beta in the brain, we studied the expression of the genes encoding for IL-1 beta, the signal-transducing IL-1 receptor type I (IL-1RI) and inducible NO synthase (iNOS) constitutively and during systemic inflammation in vascular and perivascular regions of the rat brain. Our results show that IL-1RI is constitutively expressed at the interface of the vascular wall and perivascular glia. During systemic inflammation there is induction of IL-1 beta gene expression in the vascular wall, accompanied by perivascular induction of iNOS mRNA. We conclude that during systemic inflammation vascular IL-1 beta, binding to vascular and perivascular IL-1RI receptors, may induce perivascular iNOS gene expression, leading to the production of NO and modulation of the effects of IL-1 beta in the brain. We propose that the vascular and peri-vascular induction of iNOS mRNA by IL-1 beta might represent a mechanism for the modulation of the central nervous system effects of peripheral inflammatory mediators.