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Reprogrammed macrophage tumor necrosis factor and interleukin-1 release with inflammatory pretreatment: differential
1Department of Surgery, Hennepin County Medical Center, University of Minnesota, Minneapolis 55415, USA.
Objective:
To determine whether different reprogrammed alterations in endotoxin (lipopolysaccharide, LPS)-stimulated tumor necrosis factor (TNF) and interleukin-1 (IL-1) release are seen following pretreatment with endotoxin (LPSp) or pretreatment with the particulate inflammatory stimulus zymosan.
Methods:
Murine peritoneal macrophages (M phi) pretreated for 24 hours in vitro with medium, LPSp, zymosan, latex beads, or killed Escherichia coli. After 24 hours M phi were restimulated with medium, LPSa, zymosan, latex beads, or E. coli, M phi supernatant TNF and IL-1 were measured after 24 hours and mRNA levels determined after 6 hours with reverse-transcriptase polymerase chain reaction.
Results:
Pretreatment with low dose LPSp markedly inhibited TNF release by both LPSa or zymosan, while pretreatment with zymosan increased LPSa-stimulated TNF release. Pretreatment with both LPSp and zymosan augmented LPSa and zymosan-stimulated IL-1. Zymosan pretreatment augmentation of TNF and IL-1 was accompanied by lower than basal levels of cytokine message.
Conclusion:
Reprogrammed macrophage TNF and IL-1 release was differentially regulated by distinct inflammatory stimuli. Understanding reprogrammed macrophage cytokine regulation may enable specific therapy to modify dysregulated cytokine release during sepsis and trauma.