CD200 is a cell-membrane protein expressed on several cells including neurons and endothelia. Its cognant receptor, CD200R, is primarily expressed on cells of the myeloid lineage, including microglia. It is believed that engagement of CD200 with its receptor can lead to immunosupression, thus restraining myeloid cells from tissue-damaging activation. Recent evidence from this laboratory has indicated that there is an age-related decline in CD200 expression in the hippocampus and it is suggested that this decrease could contribute to the enhanced pro-inflammatory profile observed in the brain of aged rats. The action of the inflammatory stimulus lipopolysaccharide (LPS) was investigated in mixed glia prepared from neonatal C57BL/6 wild-type (WT) and CD200-/- mice. Mixed glia were incubated in the presence or absence of LPS (1µg/ml) for 24 hours and following this, the supernatant was collected for analysis of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α by ELISA and analysis of mRNA expression of these cytokines by Q-PCR. LPS significantly increased IL-1β, IL-6 and TNF-α at mRNA and protein levels in glia prepared from WT and CD200-/- animals (p < 0.05; ANOVA; n=6). However LPS increased production of pro-inflammatory cytokines to a greater extent in mixed glial cultures prepared from CD200-/- mice compared with WT mice and the differences were statistically significant at both mRNA and protein levels (p < 0.05; ANOVA). These findings, which indicate that mixed glial prepared from CD200-/- mice were more responsive to LPS than glia prepared from WT mice and are consistent with our previous observation that interaction of CD200 with its receptor contributes to the maintenance of microglia in a quiescent state.