In these experiments, mouse recombinant IL-10 (1 ng/mL) was added 30 min prior to addition of stimulants. notably by macrophages of C57 mice, which also displayed more IL-10 than C3H macrophages. The distinct patterns of pro-inflammatory mediator production, along with TLR2/TLR1 expression, and regulation LP-211 in macrophages from Lyme disease-resistant and -susceptible mice suggests itself as a blueprint to further investigate differential pathogenesis of Lyme disease. Introduction Lyme disease, caused by infection with the spirochete often trigger immune responses directed against the spirochete and/or its lipoproteins , , , , , , , , , . The potent stimulatory properties of the spirochete and its lipoproteins are thought to be responsible for inflammatory foci in tissues, as well as other host responses against the infection, all of which have been linked to Lyme disease pathogenesis , , , , . The mouse model provides a unique opportunity to study the pathogenesis of Lyme disease, since experimental infection of different mouse strains with results in distinct disease LP-211 outcomes that bear similarities to the different Lyme disease manifestations seen in humans , . For example, C3H/HeN (or C3H/HeJ) mice develop severe arthritis (Lyme disease-susceptible) whereas C57BL/6J mice develop mild arthritis (Lyme disease-resistant) after infection with lipoproteins produced higher amounts of the prototypic IL-6 and TNF cytokines than did macrophages from disease-resistant C57 mice . We similarly reported that lymph node cells from (or its lipoproteins) in cells from mice of Lyme disease-resistant and -susceptible strains have been shown to be tightly regulated by the anti-inflammatory cytokine IL-10. studies showed that IL-10 down- regulated the production of lipoprotein-induced IL-6 and TNF in macrophages of C57 and C3H mice . Addition of exogenous IL-10 to lipopeptide-stimulated lymph-node cell cultures also reduced IFN- and IL-6 production with the inhibition being more effective LEPREL2 antibody with cells from disease-resistant C57 mice than with cells from disease-susceptible C3H mice . Studies by Brown and coworkers  revealed that lipoprotein-stimulated macrophages of C57 mice produced higher levels of the anti-inflammatory cytokine IL-10 as compared to C3H mice. studies using IL-10-/- mice of both C57 and C3H genetic backgrounds underscored the significance of IL-10 in controlling joint inflammation in Lyme disease , . Other investigators have also shown that several cytokine and chemokine genes are up regulated in joints of to live spirochetes and a lipoprotein, and to evaluate how these mediators are regulated by IL-10. Our hypothesis is LP-211 that susceptibility and resistance to Lyme disease, as modeled in mice, is associated with early induction and regulation of inflammatory mediators by innate immune cells after exposure to live spirochetes and/or LP-211 its lipoproteins. We first assessed production/transcription of cytokines and chemokines in response to stimulation with both live and LP-211 the lipoprotein outer surface protein A (L-OspA) using multiplex ELISA and qRT-PCR. Next we used qRT-PCR to assess transcriptional expression of genes encoding mediators of the TLR pathway after exposure of macrophages to these same stimuli. Finally, using the above experimental design, we assessed how the production levels of inflammatory mediators change in the presence of exogenous, or absence of endogenous IL-10. Our data suggest that the balance between Lyme disease-resistance and susceptibility correlates with, and may depend upon, a full pattern of expression of inflammatory mediators, and on the host’s genetic ability to regulate such pattern, with IL-10 being a key mediator of this process. Results Bone marrow-derived macrophages from Lyme-disease resistant and.