Statins exert various immunomodulatory effects but the underlying mechanisms remain unclear . Data from in vitro studies suggest that statins could interfere with the TLR pathway, thereby modulating the response to microbial products. However, depending on the experimental model, the net effect of statin treatment could be pro- or anti-inflammatory [25, 31]. For instance, statins could have anti-inflammatory effects through TLR down-regulation . Accordingly, we found that TLR2 gene expression down-regulation by statin within the lung could account for its anti-inflammatory effect. Interestingly, this is in line with previous findings from our group and others showing that tlr2 up-regulation within the lung of animals subjected to MV probably accounted for overreaction to its agonist including S. aureus cell wall compounds [6, 32]. In contrast, other mechanisms are probably involved within the blood, suggesting that the spleen was a surrogate for peripheral blood mononuclear cells . Moreover, the effects of statin probably depend on the molecule tested, the cell type and its environment, as well as both dose and duration of treatment prior to stimulation. Herein, we showed that despite one negative effect of atorvastatin treatment prior to pneumonia, namely the systemic release of IL-8 in MV rabbits, ex vivo experiments showed that whole blood taken from pretreated MV rabbits overreacted to HKSA stimulation in terms of IL-8 production. These findings, as well as in vitro studies, illustrate to what extent impact of statin on the inflammatory response is equivocal.