Hindawi Publishing Corporation Autoimmune Diseases Volume 2012, Article ID 404815, 6 pages doi:10.1155/2012/404815 Research Article Significant Changes in the Levels of Secreted Cytokines in Brains of Experimental Antiphospholipid Syndrome Mice Assaf Menachem, 1, 2, 3 Joab Chapman, 1, 2, 3 and Aviva Katzav 2, 3 1 Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel 2 Department of Neurology and Joseph Sagol Neuroscience Center, Sheba Medical Center, 52621 Ramat Gan, Israel 3 Sackler Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel Correspondence should be addressed to Joab Chapman, jchapman@post.tau.ac.il Received 3 October 2011; Accepted 28 November 2011 Academic Editor: Joz´ elio Freire de Carvalho Copyright © 2012 Assaf Menachem et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Antiphospholipid syndrome (APS) is characterized by thromboses and neuropsychiatric manifestations possibly linked to brain inflammation. In order to examine the levels of proinflammatory and anti-inflammatory cytokines in experimental APS (eAPS) mice brains, we measured the levels of TNF-α, IFN-γ, and IL-10 in brain homogenates (cytosolic fractions) and in brain slices (secreted level) at 6, 15, and 24 weeks after immunization. We induced eAPS by immunization of Balb/c mice with β 2 -glycoprotein I(β 2 GPI), the major autoantigen in the disease and controls with adjuvant alone. We found increased levels of secreted TNF-α in eAPS mice for the entire experiment period. Cytosolic and secreted IL-10 and IFN-γ levels in eAPS mice were lower at 6 and 15 weeks and higher at 24 weeks after immunization. The results suggest that brain disease in APS is associated with significant and complex changes in proinflammatory and anti-inflammatory cytokines. 1. Introduction The antiphospholipid (Hughes) syndrome (APS) is an autoimmune disorder, manifested by thromboembolic events (arterial and venous), recurrent spontaneous abor- tions, thrombocytopenia, and elevated titers of circulating antiphospholipid antibodies (aPL) [1]. Most aPL are autoan- tibodies directed against a complex of phospholipids and β 2 - glycoprotein I (β 2 GPI), a major cofactor in the binding of aPL, causing hypercoagulation and a proinflammatory state [2]. Many neurological manifestations have been described in the APS, but only stroke is well established and accepted as a diagnostic criterion in the disease [3]. Other neurological complications, which still need to be fully established, include seizures, ocular disturbances, dementia, migraine, transverse myelitis, and chorea [4]. A model of experimental APS (eAPS) in mice is induced by immunization with β 2 GPI [5]. Previous studies in our lab found behavioral changes in eAPS mice, which include hyperactivity/exploratory behavior and cognitive deficits [6–8]. The CNS manifestation developed over a period of 4-5 months after immunization [9]. The role of aPL in the pathogenesis of APS still needs to be elucidated. It is possible that other immune mediators, apart from autoantibodies, take part in the inflammatory and degenerative processes in the APS brain. Although APS is considered a B-cell mediated disease [10], T cells also have an important role in the induction and regulation of the disease, by secreting cytokines which modulate the immune response [11]. Cytokines can be divided into two subgroups: proinflammatory cytokines and anti-inflammatory cytokines. The course of many diseases, including several autoimmune diseases, depends upon the balance between these two subgroups [12]. Pro- inflammatory cytokines and chemokines have been reported to have an important role in the development of the clinical manifestation of APS [11, 13]. Previous clinical reports have shown increased serum levels of IL-4 and IL-6 in patients with APS [14, 15]. Another central inflammatory cytokine associated with APS is tissue necrosis factor-α (TNF-α), levels of which are known to be elevated and reflect pathological processes within the endothelial cells [15, 16].