BACKGROUND: Neuropeptide Y (NPY) may influence differentiation of Th cells. It is assumed that the immunological pathology of experimental allergic encephalomyelitis (EAE) is related to abnormal differentiation of Th cells OBJECTIVE: To investigate the effect of NPY on white matter demyelination, the serum levels interleukin-4 (IL-4) and gamma-interferon (IFN-γ), as well as EAE pathogenesis in an EAE guinea pig model following NPY injection into the lateral cerebral ventricle. DESIGN, TIME AND SETTING: A randomized controlled animal study, which was performed in the Infection Immunity Animal Laboratory, Affiliated Hospital of Luzhou Medical College, China, from October 2005 to April 2006. MATERIALS: Thirty healthy female guinea pigs of 8–12 weeks of age, and 10 healthy female rats of three months of age were used. NPY was provided by Sigma Company, USA. NPY kit was provided by Beijing Huaying Biotechnology Institute, China. METHODS: Thirty guinea pigs were randomly divided into three groups: normal control group, EAE model group, and NPY intervention group (n =10 per group). Normal control group and EAE model group: Saline (10 μL, once) was injected into the lateral cerebral ventricle. After one week, the same volume of Freund’s adjuvant complete was either injected subcutaneously into two post-palms or EAE was modeled. NPY intervention group: EAE was modeled after one week and NPY was injected (10 μL of 6 nmol NPY, once) into the lateral cerebral ventricle. Myelin basic protein (MBP) antigen made from rat spinal cord homogenate and Freund’s adjuvant complete were injected subcutaneously into both post-palms (0.2 mL per palm) to establish the EAE model. MAIN OUTCOME MEASURES: White matter demyelination of the cerebrum, cerebellum, brain stem, and spinal cord were observed by light microscopy after HE staining. Levels of serum IFN-γ and IL-4 were detected by the double antibody sandwich ABC-ELISA technique. NPY content was detected by radioimmunoassay. RESULTS: Pathological alterations in the NPY intervention groups were reduced compared to those in the EAE model group, suggesting a reduction and remission of white matter demyelination with NPY treatment. When compared to the model group, the serum IL-4 level was increased in the NPY intervention group during the high-frequent EAE stage (P < 0.01), but the serum IFN-γ level was decreased (P < 0.01). Furthermore, the EAE latency was prolonged (P < 0.01), the neurological scores were decreased in the high-frequent EAE stage (P < 0.01), and the death rate was decreased (P < 0.05). NPY content and the serum IL-4 level at the peak stage were positively correlated with those in the latent phase (r =0.863-0.900, P < 0.01), but negatively correlated with neurological scores at the peak stage (r= -0.068 to –0.863, P < 0.05–0.01). The IFN-γ level at the peak stage was negatively correlated to that in the latent phase (r = -0.683–0.650, P < 0.05), but positively correlated to neurological scores at the peak stage (r =0.975, 0.845, P < 0.05). CONCLUSION: NPY injection into the lateral cerebral ventricle can promote the secretion of IL-4, inhibit the production of IFN-γ, relieve white matter demyelination, and inhibit EAE attack in an experimental model of EAE. BACKGROUND: Neuropeptide Y (NPY) may influence differentiation of Th cells. It is assumes that the immunological pathology of experimental allergic encephalomyelitis (EAE) is related to abnormal differentiation of Th cells OBJECTIVE: To investigate the effect of NPY on white matter demyelination, the serum levels interleukin-4 (IL-4) and gamma-interferon (IFN-γ), as well as EAE pathogenesis in an EAE guinea pig model the NPY injection into the lateral cerebral ventricle. DESIGN, TIME AND SETTING: A randomized controlled animal study, which was performed in the Infection Immunity Animal Laboratory, Affiliated Hospital of Luzhou Medical College, China, from October 2005 to April 2006. MATERIALS: Thirty healthy female guinea pigs of 8-12 weeks of age, and 10 healthy female rats of three METHODS: Thirty guinea pigs were randomly divided into thre. months of age were used. NPY was provided by Sigma Company, USA. NPY kit was provided by Beijing Huaying Biotechnology Institute, China. Normal control group and EAE model group: Saline (10 μL, once) were injected into the lateral cerebral ventricle. After one week, EAE model group, and NPY intervention group (n = 10 per group) the same volume of Freund’s adjuvant complete was either injected subcutaneously into two post-palms or EAE was modeled. NPY intervention group: EAE was modeled after one week and NPY was injected (10 μL of 6 nmol NPY, once) into the lateral cerebral ventricle . Myelin basic protein (MBP) antigen made from rat spinal cord homogenate and Freund’s adjuvant complete were injected subcutaneously into both post-palms (0.2 mL per palm) to establish the EAE model. MAIN OUTCOME MEASURES: White matter demyelination of the cerebrum, cerebellum , brain stem, and spinal cord were observed by light microscopy after HE staining. Levels of serum IFN-γ and IL-4 were detected by the double antibody sandwich ABC-ELISA technique. NPY content was detected by radioimmunoassay. RESU LTS: Pathological alterations in the NPY intervention groups were reduced compared to those in the EAE model group, suggesting a reduction and remission of white matter demyelination with NPY treatment. When compared to the model group, the serum IL-4 level was increased in the NPY intervention (P <0.01), but the serum IFN-γ level was decreased (P <0.01). Furthermore, the EAE latency was prolonged (P <0.01), the neurological scores were decreased in the high -frequent EAE stage (P <0.01), and the death rate was decreased (P <0.05). NPY content and the serum IL-4 level at the peak stage were positively correlated with those in the latent phase (r = 0.863-0.900 , P <0.01), but negatively correlated with neurological scores at the peak stage (r = -0.068 to -0.863, P <0.05-0.01). The IFN-γ level at the peak stage was negatively correlated to that in the latent phase (r = -0.683-0.650, P <0.05), but positively correlated to neurological scores at t CONCLUSION: NPY injection into the lateral cerebral ventricle can promote the secretion of IL-4, inhibit the production of IFN-γ, relieve white matter demyelination, and inhibit EAE attack (r = 0.975, 0.845, in an experimental model of EAE.