ELSEVIER Neuroscience Letters 202 (1995) 17-20 N[OROSCI[HC[ IHT[IIS Interleukin-lfl and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients Doris Blum-I)egen a,*, Thomas Mtiller b, Wilfried Kuhn b, Manfred Geflach a,b, Horst Przuntek b, Peter Riederer a aDepartment af Psychiatry, Clinical Neurochemistry, University of Wiirzburg, Fiichsleinstrafle 15, 97080 Wiirzburg, Germany bDepartment of Neurology, St. Josef Hospital, University of Bochum, Bochum, Germany Received 6 October 1995; revised version received 3 November 1995; accepted 3 November 1995 Abstract Interleukin-lfl (IL-Ill), interleukin-2 (IL-2), and interleukin-6 (IL-6) were measured in the cerebrospinal fluid (CSF) and plasma of 12 control subjects, 11 sporadic Alzheimer's disease (AD) and 22 de novo Parkinson's disease (PD) patients using high sensitivity enzyme-linked immunosorbent assays (ELISA). IL-lfl and IL-6 contents were significantly elevated in the CSF of de novo PD and AD patients in comparison to the control group. In contrast, the plasma levels were not significantly affected. IL-2 contents in the CSF and plasma samples were unchanged in the three groups compared. Because the two cytokines IL-lfl and IL-6 are known to play a key role in the interaction between the nervous and immune system, e.g. in the so-called acute phase response, our results support the involve- ment of immunological e.vents in the complex process of neurodegeneration in AD and PD. Keywords: Interleukin-]/~; Interleukin-2; Interleukin-6; Parkinson's disease; Alzheimer's disease; Plasma; Cerebrospinal fluid; Enzyme-linked immuno,;orbent assay Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative disorders in the elderly. Although many different hypotheses have been advanced [9], the cause of chronic neural cell death and the underlying mechanisms remain elusive. It is now widely accepted that at least some restricted immune- related phenomena are involved in the etiology of both diseases. For instance, autoantibodies against cholinergic and dopaminergic neurons were found in AD and PD [5], respectively. Furthermore, elevated levels of major histo- compatibility complex II antigen [25] and complement proteins [24,39] in various brain areas were demonstrated in both diseases. Finally, alterations in the content of sev- eral cytokines and growth factors in the brain parenchy- ma, serum and/or cerebrospinal fluid (CSF) of AD [1,3,4, 6,14,38] and PD patients [27,28] are well-documented. Cytokines play a key role in the interaction between nervous and immune system, including cell growth and differentiation, inflammatory processes, the immune and acute phase response i l 2,31 ]. Interleukin- lfl (IL- lfl) and * Corresponding author. Tel.: +49 931 203323; fax: +49 931 203425. interleukin-6 (IL-6) are released from microglial cells and astrocytes [20]. IL- lfl stimulates the proliferation of astro- cytes, induces the release of IL-6 and regulates the syn- thesis of nerve growth factor [10,20,21]. The biological activities of IL-6 in the brain include the induction of acute phase protein synthesis, as well as the differentia- tion of neuronal cells and improvement of catecholamin- ergic and cholinergic cell survival [16,30,35]. Interleukin- 2 (IL-2) is synthesized and secreted by activated T-cells and acts as a T-cell growth factor [37]. In the brain it is known to stimulate the proliferation and maturation of oligodendrocytes [2]. In the present study, we measured IL-6 and IL-2 con- centrations in the CSF of de novo PD and AD patients for the first time. In addition, we checked the IL-lfl levels because of contradictory data about the IL-lfl contents in the CSF of AD patients [4,22,33]. In parallel, we also checked the levels of IL-lfl, IL-2, and IL-6 in the plasma of the same patients in order to compare the immunologi- cal status between periphery and CNS. Paired blood and CSF samples were taken simultane- ously between 0800 h and 1000 h. Blood samples were 0304-3940/95/$09.50 © 1995 Elsevier Science Ireland Ltd. All rights reserved SSDI 0304-3940(95)12192-4