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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 β2-glycoprotein I (β2GPI), 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.