CYTOKINES, GLUCOCORTICOIDS AND LIPOCORTINS IN THE CONTROL OF NEUTROPHIL MIGRATION

By using a simple murine air-pouch technique we were able to measure an intense neutrophil infiltration in response to the local application of specific proinflammatory stimuli such as interleukin-1 and interleukin-8. The role of endogenous and exogenous lipocortin 1 on this cellular migratory response was evaluated. Exogenously i.v. administration of human recombinant lipocortin 1 and its N-terminus peptide Ac2-26 dose-dependently inhibited IL-1-induced neutrophil migration with calculated ED(50) values of 5.18+/-0.74 mu g and of 88.0+/-13.1 mu g per mouse, respectively. Direct injection of these agents into the pouch was ineffective. In keeping with these observations, the inhibitory action exerted by dexamethasone, in both IL-1- and IL-8-induced cell infiltration, was abrogated by passive immunisation of mice with specific anti-lipocortin 1 antibodies. In conclusion, lipocortin 1 is not only a mediator of some of the anti-inflammatory actions of glucocorticoid hormones, but can also modulate the effect that specific cytokines have on the trafficking of highly specialised cells like the neutrophils.