ROLE OF IL-4 IN LIMITING NEUROINFLAMMATION IN VIVO

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

Buenos Aires

Congreso; First French-Argentine Immunology Congress; 2010

Role of IL4 in limiting Neuroinflammation in vivo Javier A. Soria, Emilia Gaviglio, Daniela S. Arroyo, MC Rodriguez Galan, Pablo Iribarren Microglial cells (MC) are key immune cells within the central nervous system (CNS). They participate in CNS homeostasis being able to become activated once they contact exogenous and endogenous pro-inflammatory signals. Some CNS injuries are accompanied by cell infiltration. The recruitment of inflammatory cells contributes to tissue damage and may be critical for inducing a continuous activation of microglia. Our hypothesis is that the presence of anti-inflammatory cytokines, such as IL-4, in the CNS may regulate microglial cell activation and infiltration and activation of peripheral leucocytes, modulating neurotoxic inflammation. Here, we evaluated the effects of IL4 on the CNS inflammatory response using a model of neuroinflammation induced by systemic injection of bacterial lipopolysacharide (LPS) in IL4 KO mice. Our preliminary results indicate that after LPS injection, both groups of mice increased the numbers of MC and infiltrating cells. Although the magnitude of the increase in MC was similar in both groups, we found that after treatment IL4 KO mice showed higher numbers of recruited cells compared to non-injected controls and to WT mice, either in a basal state or after stimulation. The results indicated that monocytes/macrophages were the main cellular component of the recruited cells. We also observe the arrival of inflammatory monocytes (based on Ly6Chi expression) in both groups after LPS-stimulation. About the expression of cell surface activation molecules, after LPS-stimulus IL4 KO mice increased CD80 (p:0.0018), CD86 (p:0.0415) and CD11c (p:0.0021) compared to non-injected controls and LPS-injected WT mice. IL4 KO mice also increased MHC II after LPS, but similarly to WT. Moreover, after LPS stimulus, we observed that MC from IL4 KO mice produced higher TNFa and IL1b (protein and mRNA) compared to controls and LPS-injected WT mice. The lack of modulation in limiting infiltration to the CNS and activation of MC in IL4 KO mice, suggest that IL4 may be important in the regulation of CNS inflammatory response in vivo.