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Interleukin-8 Is Produced in Neoplastic and Infectious Diseases of the Human Central Nervous System¹

Neurosurgery Service, University Hospital (CHUV), 1011 Lausanne, Switzerland [E. V. M., E. G., I. D., N. d. T.]; Theodor Kocher Institut, Universitat Bern, 3000 Bern, Switzerland [A. W.]; Sandoz Forschungsinstitut, Vienna, Austria [M. C., F. E.]; Section of Clinical Immunology, University Hospital, 8044 Zürich, Switzerland [K. F., A. F.]

The presence of interleukin-8 (IL-8), a leukocyte chemotactic factor, was examined in primary and metastatic central nervous system tumors and in nonneoplastic acute meningoencephalitides.

In vitro: (a) 11 of 12 glioblastoma cell lines constitutively expressed IL-8 mRNA; (b) 5 of 6 of these cell lines secreted IL-8 protein as detected by enzyme-linked immunosorbent assay and a glucosaminidase release bioassay; and (c) IL-1ß or tumor necrosis factor was able to augment both IL-8 mRNA steady state levels and protein secretion of all cell lines tested except IN-319.

IL-8 was also found in vivo. (a) IL-8 poly A⁺ mRNA was detected in 2 of 2 low grade astrocytomas, 1 of 2 anaplastic astrocytomas, and 6 of 6 glioblastomas. (b) IL-8 protein was present in the cyst fluid of 1 of 4 low grade astrocytomas, 1 anaplastic astrocytoma, 2 of 2 glioblastomas, 1 oligodendroglioma grade III, and one central nervous system cervical carcinoma metastasis. (c) The cerebrospinal fluid of 3 of 4 metastatic lymphomas, 2 of 16 glioblastomas, 1 of 2 low grade astrocytomas, but none of 3 anaplastic astrocytomas and none of 9 meningiomas contained IL-8. The presence of IL-8 was not restricted to central nervous system tumors as 2 of 2 bacterial meningitis and 5 of 5 acute viral meningitis patients contained considerable IL-8 levels in the cerebrospinal fluid. (d) Immunohistochemical analysis showed IL-8 immunoreactivity in perivascular tumor cells in 11 of 15 glioblastoma sections.

These data suggest that IL-8 secretion could be a key factor involved in the determination of the lymphoid infiltrates observed in brain tumors and the development of cerebrospinal fluid pleocytosis in meningoencephalitides.

¹ This work was supported by Grants 3.595.087 (N. d. T.) and 31.28402.90 (A. F.) of the Swiss National Science Foundation.

² To whom requests for reprints should be addressed, at Ludwig Institute for Cancer Research, 9500 Gilman Drive, San Diego, CA 92093-0660.

Received 12/11/91. Accepted 5/29/92.

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