Th1 and Th2 cytokine immunomodulation by gangliosides in experimental autoimmune encephalomyelitis Gla´ucia Monteiro de Castro, Maira Eduarda Zanin, Danielle Ventura-Oliveira, Conceic xa˜o Aparecida Vilella, Rika Ashimine, Ricardo de Lima Zollner ) Laborato ´rio de Imunologia & Alergia Experimental, Departamento de Clı´nica Me ´dica, Faculdade de Cie ˆncias Me ´dicas, Universidade Estadual de Campinas, UNICAMP, PO Box 6111, Campinas/SP 13081-970, Brazil Received 11 October 2003; received in revised form 11 February 2004; accepted 12 February 2004 Abstract In experimental autoimmune encephalomyelitis, a classical model for multiple sclerosis, the cytokines provide the necessary signals to activate specific T cells for self-antigens. Gangliosides have multiple immunomodulatory activities, decreasing the lymphoproliferative responses and modulating cytokine production. Here, we tested the effects of gangliosides on the switching of Th1 to Th2 cytokine expression, in spleen cells obtained from Lewis rats during the acute phase of EAE, and after recovery from the disease. For this purpose, total RNA from spleen cells was isolated and submitted to RT-PCR to investigate Th1 (IL-2, TNF-a, and IFN-g) and Th2/Th3 (IL-10 and TGF-b) cytokine gene expression. Results demonstrate that the group treated with gangliosides displays mild disease, with low expression of IFN-g mRNA and high TGF-b mRNA expression. We conclude that the gangliosides may modulate Th1 cells by the synthesis of cytokines shifting the profile to the Th2/Th3 phenotype. Ó 2004 Elsevier Ltd. All rights reserved. Keywords: Cytokines; EAE; Gangliosides; Immunomodulation; Multiple sclerosis 1. Introduction Multiple sclerosis (MS) is an autoimmune demyelin- ating disease of the central nervous system (CNS). CD4C Th1 cells initiate the MS inflammatory process, which leads to a secondary macrophage recruitment, and subsequent myelin destruction [1,2]. These cells cross the blood–brain barrier starting an immune reaction, which subsequently attracts a variety of nonspecific cells. Cytokine induction and release, and antibody production are followed by the activation of microglia and astrocytes [3,4]. Together, these events constitute a chronic inflammatory and demyelinating disease, resulting in CNS injury with varying degrees of neurological deficit [5]. The subject of cytokines has become a central topic within MS research. Evidence exists to suggest that these molecules play an essential role in the pathophysiology of MS, both by regulating the aberrant autoimmune response and by mediating myelin damage [6]. This disease mechanism is similar to that found in experimental autoimmune encephalomyelitis (EAE), an experimental paradigm of Th1 cell-mediated autoim- mune disease, considered an animal model of MS. EAE can be induced in susceptible animals by active sen- sitization with CNS tissue, myelin or myelin proteins or by adoptive transference of autoreactive T cells [7,8]. Other similar features shared by EAE and MS are the genetic susceptibility and cytokine pattern displayed during the inflammatory immune response at the demyelinating lesions [9]. Cytokines have a key role in the EAE process pro- viding the necessary signals to activate T cell specificity against self-antigens. There is overwhelming evidence to suggest that the T cells mediating EAE are of the Th1 phenotype, producing interleukin-2 (IL-2), interferon-g ) Corresponding author. Tel./fax: C55-19-32893709. E-mail address: zollner@unicamp.br (R. de Lima Zollner). Cytokine 26 (2004) 155–163 www.elsevier.com/locate/jnlabr/ycyto 1043-4666/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.cyto.2004.02.009