The weaker modulating effects of GP on the LPS-induced immune response observed in this study, may be attributed to delicately balanced differences in signaling pathways between LPS and TSST-1 [43-45]. TSST-1 has been shown to use the PI3K pathway for signaling [44] and this effect may be sustained by GP treatment [22,37]. It has been demonstrated that in septic/LPS-adapted leukocytes the PI3K pathway selectively controls sIL-1RA but not IL-1β production [48]. Signaling via PI3K has been reported to be involved in the activation of NFAT in T cells [49]. Activation of NFκB can also take place via PI3K [50], which may offer an explanation for a difference in signaling between GP (PI3K) and LPS (mitogen-activated kinase signaling). This idea may be supported by another study showing that despite the use of similar PRR, LPS and peptidoglycan activated the IL-1RA gene through different mechanisms/DNA-binding proteins and acted synergistically in combination, suggestive of signals which are not equivalent in all parts [51].