The antimicrobial peptide LL37 and its truncated derivatives potentiates proinflammatory cytokine induction by lipoteichoic acid in whole blood

Interactions of bacterial and host products in activating the innate immune system is an important area to address. The role of lipoteichoic acid (LTA) in these interactions is particularly important because it is understudied in comparison to other factors. This study evaluated the effect of cationic peptides (CPs) on LTA-induced proinfl ammatory cytokine production in human whole blood and on purifi ed leukocytes. Four different CPs of truncated derivatives from the known peptides LL37, BPI, and CP207 were used. Two of the CPs (IG33 and LL33), derivatives from LL37, potentiated S. aureus LTA induced TNF α , IL-6 and IL-1 β production in whole blood. The release of TNF α was increased 30-fold after 16 hours incubation. Intact LL37 also increased LTA-induced TNF α and IL-1 β in a time dependent manner. LTA in combination with either LL33 or IG23 demonstrated a synergistic enhanced TNF α and IL-1 β secretion on isolated leukocytes but not on purifi ed monocytes. When complexed with IG23 and LL33, the electrophoretic mobility of LTA was altered in a nondenaturating gel electrophoresis. LTA was disaggregated and migrated more rapidly, suggesting an amphiphilic effect of CPs on LTA. In conclusion, LTA synergizes with LL37 and its truncated derivatives and this may lead to proinfl ammatory cytokine production and cause problems in sepsis therapy.