Blood-borne interleukin-1 alpha is transported across the endothelial blood-spinal cord barrier of mice.
Abstract
1. Previous work has shown that one mechanism by which blood-borne interleukin-1 alpha (IL-1) may be able to affect the central nervous system (CNS) is by direct transport into the brain across the blood-brain barrier (BBB). The BBB of the brain consists of endothelial (between blood and interstitial fluid) and ependymal (between blood and cerebrospinal fluid) barriers. Which of these barriers IL-1 can cross has not previously been investigated. At the spinal cord, which could be the site of action for some of the effects of IL-1 such as analgesia, the BBB consists only of the endothelial barrier. 2. We show here that IL-1 labelled with 125I (I-IL) is transported across the BBB of the spinal cord by a saturable system similar to the one previously described for the brain. High performance liquid chromatography (HPLC) showed that most of the material entering the spinal cord represented intact I-IL. The BBB of the spinal cord was no more leaky to radioactively labelled albumin than the BBB of the brain and was not disrupted by 50 micrograms kg-1 of IL-1. 3. Capillary depletion showed that most of the I-IL entered the parenchymal-interstitial fluid space of the spinal cord with only a modest amount being sequestered by the endothelial cells of its BBB. 4. I-IL entered the cervical, thoracic and lumbar regions of the spinal cord equally well. I-IL entering at the brain and diffusing caudally was estimated only to account for about 1% of the total radioactivity found in the spinal cord after i.v. injection.(ABSTRACT TRUNCATED AT 250 WORDS)
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- Banks WA, Broadwell RD. Blood to brain and brain to blood passage of native horseradish peroxidase, wheat germ agglutinin, and albumin: pharmacokinetic and morphological assessments. J Neurochem. 1994 Jun;62(6):2404–2419. [PubMed] [Google Scholar]
- Banks WA, Kastin AJ. Quantifying carrier-mediated transport of peptides from the brain to the blood. Methods Enzymol. 1989;168:652–660. [PubMed] [Google Scholar]
- Banks WA, Kastin AJ. Blood to brain transport of interleukin links the immune and central nervous systems. Life Sci. 1991;48(25):PL117–PL121. [PubMed] [Google Scholar]
- Banks WA, Kastin AJ. The interleukins-1 alpha, -1 beta, and -2 do not acutely disrupt the murine blood-brain barrier. Int J Immunopharmacol. 1992 May;14(4):629–636. [PubMed] [Google Scholar]
- Banks WA, Kastin AJ, Durham DA. Bidirectional transport of interleukin-1 alpha across the blood-brain barrier. Brain Res Bull. 1989 Dec;23(6):433–437. [PubMed] [Google Scholar]
- Banks WA, Kastin AJ, Gutierrez EG. Interleukin-1 alpha in blood has direct access to cortical brain cells. Neurosci Lett. 1993 Nov 26;163(1):41–44. [PubMed] [Google Scholar]
- Banks WA, Kastin AJ, Radulovic S, Conley FK, Johnson DL, Schally AV. Selective uptake of the somatostatin analog RC-160 across the blood-brain tumor barrier of mice with KHT sarcomas. Anticancer Drugs. 1992 Oct;3(5):519–523. [PubMed] [Google Scholar]
- Banks WA, Ortiz L, Plotkin SR, Kastin AJ. Human interleukin (IL) 1 alpha, murine IL-1 alpha and murine IL-1 beta are transported from blood to brain in the mouse by a shared saturable mechanism. J Pharmacol Exp Ther. 1991 Dec;259(3):988–996. [PubMed] [Google Scholar]
- Breder CD, Dinarello CA, Saper CB. Interleukin-1 immunoreactive innervation of the human hypothalamus. Science. 1988 Apr 15;240(4850):321–324. [PubMed] [Google Scholar]
- Butter C, Baker D, O'Neill JK, Turk JL. Mononuclear cell trafficking and plasma protein extravasation into the CNS during chronic relapsing experimental allergic encephalomyelitis in Biozzi AB/H mice. J Neurol Sci. 1991 Jul;104(1):9–12. [PubMed] [Google Scholar]
- Ellison MD, Povlishock JT, Merchant RE. Blood-brain barrier dysfunction in cats following recombinant interleukin-2 infusion. Cancer Res. 1987 Nov 1;47(21):5765–5770. [PubMed] [Google Scholar]
- GRUNDY HF. Circulation of cerebrospinal fluid in the spinal region of the cat. J Physiol. 1962 Oct;163:457–465. [PMC free article] [PubMed] [Google Scholar]
- Gutierrez EG, Banks WA, Kastin AJ. Murine tumor necrosis factor alpha is transported from blood to brain in the mouse. J Neuroimmunol. 1993 Sep;47(2):169–176. [PubMed] [Google Scholar]
- Hashimoto M, Ishikawa Y, Yokota S, Goto F, Bando T, Sakakibara Y, Iriki M. Action site of circulating interleukin-1 on the rabbit brain. Brain Res. 1991 Feb 1;540(1-2):217–223. [PubMed] [Google Scholar]
- Jacobs CA, Baker PE, Roux ER, Picha KS, Toivola B, Waugh S, Kennedy MK. Experimental autoimmune encephalomyelitis is exacerbated by IL-1 alpha and suppressed by soluble IL-1 receptor. J Immunol. 1991 May 1;146(9):2983–2989. [PubMed] [Google Scholar]
- Jacques L, Couture R. Studies on the vascular permeability induced by intrathecal substance P and bradykinin in the rat. Eur J Pharmacol. 1990 Aug 2;184(1):9–20. [PubMed] [Google Scholar]
- Katsuura G, Arimura A, Koves K, Gottschall PE. Involvement of organum vasculosum of lamina terminalis and preoptic area in interleukin 1 beta-induced ACTH release. Am J Physiol. 1990 Jan;258(1 Pt 1):E163–E171. [PubMed] [Google Scholar]
- Kennedy MK, Torrance DS, Picha KS, Mohler KM. Analysis of cytokine mRNA expression in the central nervous system of mice with experimental autoimmune encephalomyelitis reveals that IL-10 mRNA expression correlates with recovery. J Immunol. 1992 Oct 1;149(7):2496–2505. [PubMed] [Google Scholar]
- Kobiler D, Lustig S, Gozes Y, Ben-Nathan D, Akov Y. Sodium dodecylsulphate induces a breach in the blood-brain barrier and enables a West Nile virus variant to penetrate into mouse brain. Brain Res. 1989 Sep 4;496(1-2):314–316. [PubMed] [Google Scholar]
- Long JB, Rigamonti DD, Dosaka K, Kraimer JM, Martinez-Arizala A. Somatostatin causes vasoconstriction, reduces blood flow and increases vascular permeability in the rat central nervous system. J Pharmacol Exp Ther. 1992 Mar;260(3):1425–1432. [PubMed] [Google Scholar]
- Nakamura H, Nakanishi K, Kita A, Kadokawa T. Interleukin-1 induces analgesia in mice by a central action. Eur J Pharmacol. 1988 Apr 27;149(1-2):49–54. [PubMed] [Google Scholar]
- Patlak CS, Blasberg RG, Fenstermacher JD. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab. 1983 Mar;3(1):1–7. [PubMed] [Google Scholar]
- Plata-Salamán CR. Immunoregulators in the nervous system. Neurosci Biobehav Rev. 1991 Summer;15(2):185–215. [PubMed] [Google Scholar]
- Rosenstein M, Ettinghausen SE, Rosenberg SA. Extravasation of intravascular fluid mediated by the systemic administration of recombinant interleukin 2. J Immunol. 1986 Sep 1;137(5):1735–1742. [PubMed] [Google Scholar]
- Sharief MK, Noori MA, Ciardi M, Cirelli A, Thompson EJ. Increased levels of circulating ICAM-1 in serum and cerebrospinal fluid of patients with active multiple sclerosis. Correlation with TNF-alpha and blood-brain barrier damage. J Neuroimmunol. 1993 Mar;43(1-2):15–21. [PubMed] [Google Scholar]
- Sirko S, Bishai I, Coceani F. Prostaglandin formation in the hypothalamus in vivo: effect of pyrogens. Am J Physiol. 1989 Mar;256(3 Pt 2):R616–R624. [PubMed] [Google Scholar]
- Triguero D, Buciak J, Pardridge WM. Capillary depletion method for quantification of blood-brain barrier transport of circulating peptides and plasma proteins. J Neurochem. 1990 Jun;54(6):1882–1888. [PubMed] [Google Scholar]
