Reprogrammed macrophage tumor necrosis factor and interleukin-1 release with inflammatory pretreatment: differential regulation by endotoxin and zymosan.

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.