Conventional
antibiotics exhibit immunomodulatory properties beneficial in the treatment of
sepsis.
Antibiotic-resistant Gram-positive bacteria have become a problem in
sepsis therapy, giving rise to increased use of last-resort
antibiotics; for example,
linezolid (LIN),
vancomycin (VAN) and
daptomycin (DAP). As the immunomodulatory properties of these
antibiotics in treating
sepsis are unknown, this study examined the effect of VAN, LIN and DAP on the immune response under
sepsis-like conditions in vitro.
Lipopolysaccharide (LPS)-activated THP-1 monocytes were incubated with LIN, VAN or DAP. Gene expression of
cytokines (TNFα, IL-1β, IL-6, IL-10) and
Toll-like receptors (TLR1, 2, 4, 6, 7 and 9) was monitored and phagocytosis was determined following coincubation with E. coli. The
antibiotics differentially modulated the gene expression of the investigated
cytokines. While LIN and VAN upregulated the expression of all TLRs, DAP downregulated
mRNA levels of TLR1, TLR2 and TLR6, which recognize
pathogen-associated molecular patterns from Gram-positive bacteria. In addition, LIN inhibited, whereas VAN promoted the phagocytic activity of monocytes. Our results suggest that LIN and VAN possess pro-inflammatory properties, whereas DAP might reduce the immune response to Gram-positive bacteria in
sepsis. Furthermore, VAN might be beneficial in the prevention of Gram-negative
infections by increasing the phagocytosis of E. coli.