REGULATION OF MICROGLIAL CELL CYTOKINE PRODUCTION BY TYPE 2 CYTOKINES

GAVIGLIO, EA; SORIA, JA; ARROYO, DS; RODRIGUEZ-GALÁN, MC E IRIBARREN, P

Buenos Aires

Congreso; First French-Argentine Immunology Congress; 2010

REGULATION OF MICROGLIAL CELL CYTOKINE PRODUCTION BY TYPE 2 CYTOKINES Gaviglio, Emilia A.; Soria, Javier A.; Arroyo, Daniela S.; Iribarren, Pablo CIBICI-CONICET. Departamento de Bioquímica Clínica. Facultad de Ciencias Químicas. UNC. Córdoba. Argentina. Inflammation plays an important role in central nervous system (CNS) infection and the progression of neurodegenerative diseases. Microglial cells are phagocytic myeloid cells located in the nervous parenchyma playing a key role in the initiation, progression and resolution of neuroinflammation. It is well known that microglial cells play a key role in mediating inflammatory processes in the CNS, which are associated with various neurodegenerative diseases. Given the potential beneficial effects of anti-inflammatory drugs and cytokines on the treatment and prevention of neurodegenerative diseases, we investigated the role of IL-4 and IL-13 in the regulation of cytokine production by microglial cells. First of all, we evaluated the effects of stimulation of mouse microglial cell lines with IL-4, IL-13 or INF-gamma, on the production of TNFalpha, IL-10 and IL-27. Both, IL-4 and IL-13 failed to induce the secretion of TNFalpha or IL-27 (p NS). However, IL-4 induced the secretion of the anti-inflammatory cytokine IL-10. In another set of experiments we tested if IL-4 or IL-13 were capable to inhibit the cytokine production of microglial cells activated by pro-inflammatory molecules, such as lipopolysaccharide (LPS) and INFgamma. We found that IL-4 inhibited the production of IL-6 on LPS-stimulated microglial cells (p<0.01). The effect of IL-4 was blocked by a monoclonal antibody specific to IL-4 (p<0.01). These preliminary results suggest that type 2 cytokines are effective modulators of cytokine production by activated microglial cells, than inducers of cytokine production in resting microglial cells. Interestingly, it seems that IL-4 is able to selectively induce the secretion of IL-10, a molecule important in the resolution of inflammation. Additional experiments are currently performed to evaluate the effects of Type 2 cytokines on the production of neurotrophic factors.