The protective and therapeutic mechanism of
bee venom acupuncture (BVA) in
neurodegenerative disorders is not clear. We investigated whether treatment with BVA (0.25 and 0.8 mg/kg) at the Zusanli (ST36)
acupoints, located lateral from the anterior border of the tibia, has a beneficial effect in a
myelin basic protein (MBP)(68-82)-induced acute
experimental autoimmune encephalomyelitis (EAE) rat model. Pretreatment (every 3 days from 1 h before immunization) with BVA was more effective than posttreatment (daily after immunization) with BVA with respect to clinical signs (neurological impairment and loss of
body weight) of acute EAE rats. Treatment with BVA at the ST36
acupoint in normal rats did not induce the clinical signs. Pretreatment with BVA suppressed
demyelination, glial activation, expression of
cytokines [
interferon (IFN)-γ,
IL-17,
IL-17A,
tumor necrosis factor-alpha (TNF-α), and IL-1β],
chemokines [
RANTES,
monocyte chemotactic protein-1 (MCP-1), and
macrophage inflammatory protein (MIP)-1α], and
inducible nitric oxide synthase (iNOS), and activation of
p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB (p65 and phospho-IκBα) signaling pathways in the spinal cord of acute EAE rats. Pretreatment with BVA decreased the number of CD4(+), CD4(+)/IFN-γ(+), and CD4(+)/IL-17(+) T cells, but increased the number of CD4(+)/Foxp3(+) T cells in the spinal cord and lymph nodes of acute EAE rats. Treatment with BVA at six placebo
acupoints (SP9, GB39, and four non-
acupoints) did not have a positive effect in acute EAE rats. Interestingly, onset and posttreatment with BVA at the ST36
acupoint markedly attenuated neurological impairment in
myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced chronic EAE mice compared to treatment with BVA at six placebo
acupoints. Our findings strongly suggest that treatment with BVA with ST36
acupoint could delay or attenuate the development and progression of EAE by upregulating regulatory T cells and suppressing T-helper (Th) 17 and Th1 responses. These results warrant further investigation of BVA as a treatment for autoimmune disorders of the central nervous system.