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Systemic administration of interleukin‐2 inhibits inflammatory neutrophil migration: role of nitric oxide
Author(s) -
Moreno Susana E,
AlvesFilho José C,
Bertozi Giuliana,
Alfaya Tais M,
Thèze Jacques,
Ferreira Sergio H,
Vargaftig Bernardo Boris
Publication year - 2006
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706835
Subject(s) - nitric oxide , proinflammatory cytokine , inflammation , medicine , infiltration (hvac) , peritoneum , immunology , pharmacology , interleukin 6 , microcirculation , cytokine , nitric oxide synthase , intravital microscopy , interleukin , pathology , physics , thermodynamics
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‐ α and IL‐1 β , 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.British Journal of Pharmacology (2006) 148 , 1060–1066. doi: 10.1038/sj.bjp.0706835