Ratio of local to systemic chemokine concentrations regulates neutrophil recruitment

CXC chemokines are important regulators of local neutrophil recruitment. In this study, we examined the role of the ratio of local to systemic chemoki ne concentrations as a significant factor determining local neutrophil recr uitment, Thioglycollate was injected intraperitoneally into BALB/c mice res ulting in a dose-dependent increase in neutrophil recruitment and local inf lammation, as measured by peritoneal levels of interleukin 6, At the high d ose of 3% thioglycollate, antibody inhibition of the murine chemokines KC a nd macrophage inflammatory protein-2 caused a reduction in peritoneal neutr ophil recruitment by as much as 93% A paradoxical effect was observed with a 0.3% thioglycollate intraperitoneal challenge. In this situation, inhibit ion of KC resulted in a significant increase in peritoneal neutrophils, and inhibition of macrophage inflammatory protein-2 also resulted in increased peritoneal neutrophils. These results were consistent with a reverse chemo tactic gradient as described by the ratio of peritoneal to plasma KC levels . A higher ratio (ie, increased peritoneal chemokines compared to plasma) r esulted in increased neutrophil recruitment after either the 3% or 0.3% thi oglycollate challenge. Our results demonstrate that whereas sufficient loca l concentrations of chemokines are necessary, a critical factor dictating l ocal neutrophil recruitment is the ratio of the local to the systemic chemo kine concentrations.