CONICET | Buscador de Institutos y Recursos Humanos

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 and the recruitment of inflammatory cells could contribute to tissue damage and may be critical for inducing persistent activation of MC. Our hypothesis is that anti-inflammatory cytokines, such as IL-4, may regulate microglial cell activation and infiltration and activation of peripheral leucocytes in the CNS. Here, we evaluated the impact of the absence of IL4 on CNS inflammatory responses induced by systemic injection of bacterial lipopolysacharide (LPS) in IL4 KO mice. Our preliminary results indicated that after LPS injection, both IL-4 KO and WT mice increased the numbers of MC and infiltrating cells. Although, the magnitude of the increases in MC were similar in both groups, the number of recruited cells before and after LPS injection seems higher in IL4 KO than in WT mice (statistical significance is currently tested). The results indicated that monocytes/macrophages were the main cellular component of the recruited cells showing phenotypical features of inflammatory monocytes (based on Ly6Chi expression), both in LPS-injected IL-4 KO and WT groups (both p<0.01 vs mock-injected). Interestingly, parenchymal MC from LPS-injected IL-4 KO mice showed increased levels of CD80 (p<0.002), CD86 (p<0.05) and CD11c (p<0.003) compared with WT controls. Moreover, after LPS stimulation, MC from IL4 KO mice produced higher levels of TNFa and IL1b (protein and mRNA) compared to WT mice. The enhanced activation of MC observed in IL4 KO mice suggests that this cytokine may be important in the regulation of CNS inflammatory response in vivo