Effects of cannabidiol on Th1/Th2 immunobalance and delayed-type hypersensitivity in ovalbumin-sensitized BALB/c mice
Date Issued
2009
Date
2009
Author(s)
Hu, Chieh-Min
Abstract
Cannabidiol (CBD) has been shown to exhibit immunosuppressive and immunomodulatory effects. However, the effect of CBD on Th1/Th2 immunobalance remains to be fully elucidated.s delayed-type hypersensitivity (DTH) reaction is an antigen-specific T cell-mediated immune response, DTH animal models are appropriate for studying the underlying mechanisms of CBD actions on both antigen-specific immune response and anti-inflammatory effects. For example, the foot pad swelling assessment of mice sensitized and challenged with a T-cell dependent protein antigen, ovalbumin (OVA) is a suitable animal model to investigate the underlying mechanisms of CBD-mediated effects on DTH. The present study aimed to investigate the effect of CBD on the Th1/Th2 immunobalance and DTH. The results of the present in vitro study indicated that direct CBD treatment attenuated OVA-induced IFN-γ produced by murine splenocytes, whereas OVA-induced IL-4 was not affected. Further, we showed that CBD administration induced a marked attenuation in the degree of food pad edema in a murine DTH model. Concordantly, the production of OVA-specific IFN-γ by splenocytes was significantly suppressed by CBD (1 mg/kg) administration; while CBD (10 mg/kg) increased OVA-induced IL-10 production. Collectively both in vitro and inivo results suggest a marked suppression of CBD on Th1 immune responses, whereas the Th2 profile was relatively unaffected. Moreover, direct CBD treatment decreased FN-γ mRNA expression, whereas IL-4 was relatively unaffected. CBD (1 mg/kg) administration showed a diminishment in IFN-γ and IL-12 mRNA expression. On thether hand, we showed that CBD diminished CD3+ T cell and F4/80+ macrophage infiltration in foot pads and inhibited the secreting of IFN-γ by T cells. Recent reports have shown that glutathione (GSH) depletion in dendritic cells shift Th1 immune response toward Th2 direction by inhibiting their ability to secret IL-12. Moreover, wereviously reported that lymphocytes are sensitive to CBD-induced apoptosis possibly through the oxidative stress in parallel with GSH diminishment. Based on these reportsnd decreased IL-12 mRNA by CBD treatment in the present study, we further hypothesized that CBD inhibited Th1 immune response through diminishing GSH level in dendritic cells. However, CBD administration did not affect GSH level in APCs in the present study. The mechanisms of CBD immunomodulatory effect shifting Th1 immune response toward Th2 remain to be further investigated.
Subjects
cannabidiol
immunomodulatory
antigen-specific
T cell
cytokine
glutathione
Type
thesis
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