Interleukin-2 inhibits eosinophil migration but is counteracted by IL-5 priming.
Conflicting data on the role of interleukin-2 in the recruitment of eosinophil granulocytes (EOS) to sites of inflammation have been presented. The objective of the present study was to investigate the effect of recombinant human IL-2 and anti-IL-2 on the migration of purified blood EOS. Neutralizing antibodies to IL-2 were added to a cytokine mixture with significant eosinophil chemotactic activity (ECA), and afterwards the ECA was tested on EOS from both normal and allergic donors. EOS migration was measured by a modification of the Boyden technique, using a 48-well microchemotaxis chamber. Recombinant human IL-2 was either added to the lower compartment of the chemotaxis chamber, or to the EOS for a pre-incubation period of 20 min, before migration assays towards the chemotaxins were performed. Anti-IL-2 caused a significant increase of EOS migration towards the cytokine mixture. Pre-incubation of the EOS with rhIL-2 inhibited the chemotaxis towards RANTES, PAF, IL-8 and eotaxin, and EOS migration towards IL-2 was lower than that towards buffer. These effects were more pronounced on EOS from normal than from allergic donors. Priming of the EOS with IL-5 prevented the inhibitory effect of IL-2. We hypothesize that IL-2 acts as an autocrine regulator of EOS migration, and that this inhibitory effect may be downregulated in allergy, allowing an increased migration of EOS towards chemotactic factors.
Lampinen
M
M
Asthma Research Centre, University Hospital, S-751 85 Uppsala, Sweden. maria.lampinen@medsci.uu.se
Håkansson
L
L
Venge
P
P
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D015848:Interleukin-5