Autoimmunity as a Complication of Interleukin 2 Immunotherapy

Gaspari, Anthony A.

doi:10.1001/archderm.1994.01690070088014

Cited by 7 publications

(2 citation statements)

References 37 publications

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“…When used on a more chronic basis, such effect may contribute to the migration of inflammatory cells, mostly lymphocytes, to the perivascular site. A number of side effects observed with IFNα have been described with IL-2 (Gaspari, 1994), including the induction of chronic arthritis, myositis, and thyroid manifestations.…”

Section: Autoimmune Manifestations With Cytokine Administrationmentioning

confidence: 99%

Molecular Autoimmunity

2005

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Section: Autoimmune Manifestations With Cytokine Administrationmentioning

confidence: 99%

Molecular Autoimmunity

2005

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“…Bearing in mind the multiple effects that IL-2 has on immune, endocrine, glial, and neuronal cells, IL-%induced neurotoxicity may likely also involve mechanisms that cannot be reflected by in vitro models. For instance, in vivo administration or increased expression of IL-2 has generally been found to trigger or assist in the abrogation of immunological tolerance (Carrieri et al, 1992;Gaspari, 1994;Heath et al, 1992;Kroemer et al, 1991;Opdenakker and Van Damme, 1994;Schattner, 1994).…”

Section: The Brain Il-2dl-2r System Participates Inmentioning

confidence: 99%

Neurotoxicity induced by interleukin-2: Involvement of infiltrating immune cells

Hanisch

Neuhaus

Quirion

et al. 1996

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Interleukin-2 (IL-2), a key regulator of immune functions, also has potent effects on neurons and glia. IL-2 modulates neural cell growth and survival and transmitter and hormone releases and is thought to mediate neuroimmune interactions. Investigating the neuroendocrine consequences of chronically elevated central nervous system (CNS) levels of IL-2, we recently observed marked neurotoxicity [Hanisch et al. (1994) Endocrinology 135:2465-2472]. In the present study, we characterize in detail the modifications in brain tissue architecture as they result in Sprague-Dawley rats from intracerebroventricular (i.c.v.) administration of low amounts of IL-2 (5 and 15 U/h, respectively, delivered by means of osmotic minipumps for up to 14 days). Histological inspection of the brains revealed massive cellular infiltrates in the ipsilateral hemisphere. The infiltrates were associated with pronounced angiogenesis and changes in the composition of the extracellular matrix. These anatomical changes apparently developed between day 7 and 14. They were specific for IL-2 and were not seen in animals treated, for example, with heat-inactivated IL-2 (controls). We further show that chronic central administration of IL-2 let to T and B lymphocyte invasion of the brain and an intracranial agglomeration of large numbers of MHC class II-positive cells. Immunocytochemistry revealed a widespread inundation of CNS tissue and a decoration of glial cells and neurons by endogenous antibodies. Tissue regions around the IL-2-induced infiltrates showed myelin destruction and neuronal cell loss. Chronically elevated CNS levels of IL-2 may, thus, not only interfere with neurotransmission and endocrine functions but also severely disturb tissue homeostasis. Therefore, the present findings could be relevant to brain injuries, CNS disorders, and clinical treatments associated with increased IL-2 levels or involving an immune component.

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