1.
Interleukin-2 (IL-2) has
proinflammatory properties that limit its therapeutic use. Its side effects are mainly explained by the induction of a vascular leakage
syndrome.
Cytokines, as
TNF-alpha and
IL-1beta, and
nitric oxide (NO) generated by IL-2-activated
leukocytes play a role in this defect. 2. As the systemic release of these mediators inhibits
neutrophil migration to a specific
inflammatory site, we investigated now whether IL-2 administrated systemically inhibits the
neutrophil recruitment to the
inflamed peritoneum. The involvement of NO in the process was also addressed. 3. Using
peritoneal neutrophils, we show that the
intravenous treatment of the
mice with IL-2 inhibits the
neutrophil migration induced by
carrageenin, LPS or fMLP. In confirmation, IL-2-treated
mice showed a
significant reduction in
leukocyte rolling and
adhesion in
mesenteric microcirculation evaluated after
carrageenin, LPS and fMLP injections. Aminoguanidine prevented the
inhibitory effect of IL-2 on carrageenin-induced
neutrophil migration, rolling and
adhesion. In contrast, IL-2 failed to reduce the
lung leukocyte infiltration induced by LPS. Therefore, IL-2 inhibition of
neutrophil migration is
organ specific. 4. Our results indicate that IL-2 administered systemically inhibits
neutrophil recruitment to some
inflammatory sites through a mechanism dependent on NO. The results also reinforce the needs to determine the mechanism by which patients treated with IL-2 show increased risks of
infection.
