DISTINCT REGULATION OF IL-8 AND MCP-1 BY LPS AND INTERFERON-GAMMA-TREATED HUMAN PERITONEAL-MACROPHAGES

Background. Interleukin-8 and monocyte chemotactic protein-1 (MCP-1) a re major leukocyte chemoattractants during bacterial peritonitis by re cruiting neutrophils and monocytes/macrophages respectively. Methods. Peritoneal macrophages (PM) from 12 different CAPD patients with perit onitis were stimulated with either 10 ng/ml LPS, 10 ng/ml IFN-gamma or LPS+IFN-gamma, and IL-8 and MCP-1 production was determined on protei n and mRNA levels by using ELISA technique and Northern blot analysis. To obtain information from two different stages of activation, experi ments were done with highly activated PM directly after isolation and with cells after 10 days in culture, each group being stimulated for 4 h. Unstimulated cells served as control. Results. Immediately after is olation IL-8 mRNA-expression and synthesis was high and could be furth er increased by LPS stimulation, whereas IFN-gamma treatment showed no significant influence. The levels of MCP-1 were also initially high b ut could not be further stimulated by LPS, whereas addition of IFN-gam ma, resulted in a significant rise in MCP-1 synthesis. After 10 days i n culture LPS-stimulation of cells again revealed a significant increa se in IL-8 protein synthesis, whereas IFN-gamma showed no effect. LPS anergy for MCP-1 was still seen in PM after 10 days in culture, and IF N-gamma, treatment again induced a significant rise in MCP-1 synthesis . The overall production of both chemokines was far higher on day 1 co mpared to day 10. Conclusion. Our data show differences in LPS/IFN-gam ma regulation for IL-8 and MCP-1 in both highly activated and in resti ng, mature peritoneal macrophages, suggesting distinct pathways for th ese chemokines that may offer a means of control for the specific recr uitment of neutrophils and monocytes/macrophages in bacterial peritoni tis.