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

Abstract Human interleukin-1α is transported across the murine blood–brain barrier (BBB) and blood–testis barrier (BTB) by a saturable transport system. Differences in the biological activity and binding of human IL-1 in mouse and rat brain raise the possibility of species differences in the transport of IL-1 across the BBB and BTB. We measured the transport of recombinant human 125 I-IL-1α (I-huIL-1α) and rat 125 I-IL-1α (I-ratIL-1α) across the rat BBB and BTB after intravenous injection using a sensitive in vivo technique and film autoradiography. I-ratIL-1α was found to cross the rat BBB and rat BTB at rates comparable to those reported previously for murine IL-1α in mice. Passage across the BBB was inhibited by the addition of unlabeled rat IL-1α, demonstrating saturable transport. In contrast, I-huIL-1α entered the brain of the rat much more slowly, and its entry was not inhibited by the addition of unlabeled human IL-1α. These results show that the rat interleukin-1 transporter, unlike the murine transporter, does not transport human IL-1α. This difference highlights the importance of species specificity in IL-1α transport and may partly explain the different physiological responses to exogenous human IL-1α among rodent species.