title: Anandamide prior to sensitization increases cell-mediated immunity in mice.
abstract: The endocannabinoid system has become a topic of great interest in pharmacology due to its remarkable distribution in mammal organisms and capacity to play a modulatory role on several physiological systems, including modulation of immunity. Many studies have shown that administration of cannabinoids causes inhibitory effects on immune cells, including decreased proliferation and antigen-presenting cell (APC) co-stimulatory activity. In contrast, other groups have shown that some cannabinoids might present stimulatory actions on macrophage activity and T cell activation. Therefore, we aimed to investigate whether a treatment in vivo with a low dose of anandamide (0.1mg/kg) immediately prior to sensitization would have an immunosuppressive or immunostimulatory effect on cell-mediated immunity (Th1 response) in mice. We report here that anandamide, prior to sensitization, was able to increase the Th1 response to ovalbumin in vivo and ex vivo. Anandamide increased delayed type hypersensitivity (DTH), splenocyte proliferation, and IFN-gamma production in a co-culture of adherent and non-adherent splenocytes. Moreover, anandamide prior to sensitization increased both the expression of DC co-stimulatory molecules (CD80/CD86) and IL-12/IL23 (p40) production ex vivo. We have also assessed direct effects of anandamide in the IFN-gamma/IL-4 balance of ConA-stimulated splenocytes in vitro. Anandamide at nanomolar concentrations increased the production of IFN-gamma, while such production decreased at micromolar range. Thus, anandamide induced both the increment of DC activation and IFN-gamma production, which are likely the mechanisms involved in the increase of Th1 response reported here.
authors.affiliation: Neuroimmunomodulation Research Group, Department of Pathology, School of Veterinary Medicine, University of São Paulo, CEP 05508-270, São Paulo, SP Brazil.
authors.forename: Alison
authors.initials: A
authors.lastname: Ribeiro
authors.forename: Viviane
authors.initials: V
authors.lastname: Ferraz-de-Paula
authors.forename: Milena L
authors.initials: ML
authors.lastname: Pinheiro
authors.forename: Mônica
authors.initials: M
authors.lastname: Sakai
authors.forename: Frederico A
authors.initials: FA
authors.lastname: Costa-Pinto
authors.forename: João
authors.initials: J
authors.lastname: Palermo-Neto
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001007:Anxiety / Q000523:psychology; D001095:Arachidonic Acids / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D063388:Endocannabinoids; D004797:Enzyme-Linked Immunosorbent Assay; D005106:Exploratory Behavior / Q000187:drug effects; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007111:Immunity, Cellular / Q000187:drug effects*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D001095:Arachidonic Acids; D016207:Cytokines; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D015847:Interleukin-4; D007371:Interferon-gamma; C078814:anandamide; D003345:Corticosterone