Differential transport of rat and human interleukin-1 alpha across the blood-brain barrier and blood-testis barrier in rats

Human interleukin-1 alpha is transported across the murine blood-brain barr ier (BBB) and blood-testis barrier (BTB) by a saturable transport system. D ifferences in the biological activity and binding of human IL-1 in mouse an d rat brain raise the possibility of species differences in the transport o f IL-I across the BBB and BTB. We measured the transport of recombinant hum an I-125-IL-1 alpha (I-huIL-1 alpha) and rat I-125-IL-1 alpha (I-ratIL-1 al pha) across the rat BBB and BTB after intravenous injection using a sensiti ve in vivo technique and film autoradiography. I-ratIL-1 alpha was found to cross the rat BBB and rat BTB at rates comparable to those reported previo usly for murine IL-1 alpha in mice. Passage across the BBB was inhibited by the addition of unlabeled rat IL-1 alpha, demonstrating saturable transpor t. In contrast, I-huIL-1 alpha entered the brain of the rat much more slowl y, and its entry was not inhibited by the addition of unlabeled human IL-1 alpha. These results show that the rat interleukin-l transporter, unlike th e murine transporter, does not transport human IL-1 alpha. This difference highlights the importance of species specificity in IL-1 alpha transport an d may partly explain the different physiological responses to exogenous hum an IL-1 alpha among rodent species. (C) 2000 Elsevier Science B.V, All righ ts reserved.