Maggot secretions suppress pro-inflammatory responses of human monocytes through elevation of cyclic AMP.
OBJECTIVE
Maggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. As monocytes may contribute to the excessive inflammatory responses in such wounds, this study focussed on the effects of maggot secretions on the pro-inflammatory activities of these cells.


METHODS
Freshly isolated monocytes were incubated with a range of secretions for 1 h and then stimulated with lipopolysaccharides (range 0-100 ng/ml) or lipoteichoic acid (range 0-5 microg/ml) for 18 h. The expression of cell surface molecules, cytokine and chemokine levels in culture supernatants, cell viability, chemotaxis, and phagocytosis and killing of Staphylococcus aureus were measured.


RESULTS
Maggot secretions dose-dependently inhibited production of the pro-inflammatory cytokines TNF-alpha, IL-12p40 and macrophage migration inhibitory factor by lipopolysaccharides- and lipoteichoic acid-stimulated monocytes, while enhancing production of the anti-inflammatory cytokine IL-10. Expression of cell surface receptors involved in pathogen recognition remained unaffected by secretions. In addition, maggot secretions altered the chemokine profile of monocytes by downregulating macrophage inflammatory protein-1beta and upregulating monocyte chemoattractant protein-1 and IL-8. Nevertheless, chemotactic responses of monocytes were inhibited by secretions. Furthermore, maggot secretions did not affect phagocytosis and intracellular killing of S. aureus by human monocytes. Finally, secretions induced a transient rise in the intracellular cyclic AMP concentration in monocytes and Rp-cyclic AMPS inhibited the effects of secretions.


CONCLUSIONS
Maggot secretions inhibit the pro-inflammatory responses of human monocytes through a cyclic AMP-dependent mechanism. Regulation of the inflammatory processes by maggots contributes to their beneficial effects on chronic wounds.
van der Plas
M J A
MJ
Department of Infectious Diseases, C5-P, Leiden University Medical Center (LUMC), Albinusdreef 2, PO Box 9600, 2300 RC, Leiden, the Netherlands.
Baldry
M
M
van Dissel
J T
JT
Jukema
G N
GN
Nibbering
P H
PH
D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004175:Diptera; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D016753:Interleukin-10 / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D007814:Larva / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000382:microbiology / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013682:Teichoic Acids / Q000494:pharmacology; D014947:Wounds and Injuries / Q000628:therapy
D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D016753:Interleukin-10; C009900:lipoteichoic acid