Differential production of chemokines and their role in neutrophil infiltration in rat allergic inflammation

Background: Recently we demonstrated that activated rat macrophages produced neutrophil chemotactic factors (chemokines) including cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2 alpha, CINC-2 beta, CINC-3/rat macrophage inflammatory protein (MIP)-2 and rat MIP-1 alpha (rMIP-1 alpha). Methods: In the present study, by using an enzyme-linked immunosorbent assay specific for each chemokine, we determined the levels of the chemokines in the pouch fluid (inflammatory site) of the fluorescein isothiocyanate-labeled ovalbumin (FITC-OVA)-induced allergic inflammation in rats. Effects of anti-chemokine antibodies on neutrophil chemotaxis were determined in vivo and in vitro. Results: CINC-1 was the major chemokine which rapidly increased after challenge with FITC-OVA, whereas CINC-3 was a minor one, and CINC-2, CINC-3 and rMIP-1 alpha increased slowly with a lag time of about 2 h. Anti-CINC-1/CINC-2 antibodies, which inhibited all the CINCs, suppressed both neutrophil infiltration in vivo and neutrophil chemotactic activity of the 8-hour pouch fluid in vitro, whereas anti-rMIP-1 alpha antibody slightly suppressed the chemotaxis in vivo and in vitro. Conclusion: Our results suggest that CINCs, especially CINC-1 and CINC-2, play an important role in the infiltration of neutrophils into the inflammatory site of FITC-OVA-induced allergic inflammation in rats.