Reprogrammed Macrophage Tumor Necrosis Factor and Interleukin-1 Release with Inflammatory Pretreatment

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Abstract
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 (LPSsub p ) or pretreatment with the particulate inflammatory stimulus zymosan. Methods Murine peritoneal macrophages (MO) pretreated for 24 hours in vitro with medium, LPSsub p , zymosan, latex beads, or killed Escherichia coli. After 24 hours MO were restimulated with medium, LPSsub a , zymosan, latex beads, or E. coli. MO 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 LPSsub p markedly inhibited TNF release by both LPSsub a or zymosan, while pretreatment with zymosan increased LPSsub a -stimulated TNF release. Pretreatment with both LPSsub p and zymosan augmented LPSsub a 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.

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