Interleukin-12 inhibits eosinophil degranulation and migration but does not promote eosinophil apoptosis.
BACKGROUND
Animal and human studies demonstrated that interleukin (IL)-12, a Th1 cytokine, reduces blood and bronchial eosinophilia, and airway hyperreactivity. According to current concepts, these effects are mediated through the release of cytokines promoting eosinophil recruitment and activation. However, the presence of IL-12 receptors on eosinophils suggests that IL-12 also acts directly on eosinophils. We postulated that IL-12 directly modulates eosinophil functions and has the capacity to regulate eosinophil degranulation, migration and survival, in vitro.


METHODS
Effects of IL- 12 on purified human blood eosinophils were evaluated for peroxidase (EPO) release, eotaxin-induced migration through a model of basement membrane (Matrigel), and survival.


RESULTS
IL-12 inhibited 50% of PAF and secretory IgA-induced EPO release (n = 8, p < 0.001). IL-12 also reduced eotaxin-induced migration through Matrigel by 54 +/-6% (n = 6, p < 0.01). These effects were not explained by an IL-12-induced impaired viability or apoptosis.


CONCLUSIONS
Our results demonstrate that IL-12 directly modulates eosinophil functions without promoting apoptosis and explain, at least in part, the effects of IL-12 on eosinophils observed in in vivo studies.
Davoine
Francis
F
Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, Canada.
Ferland
Claudine
C
Chakir
Jamila
J
Lee
Joo Eun
JE
Adamko
Darryl J
DJ
Moqbel
Redwan
R
Laviolette
Michel
M
D017209:Apoptosis / Q000187:drug effects*; D015550:Cell Degranulation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D047209:Eosinophil Peroxidase / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology; D017997:Leukotriene C4 / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology; D018123:Receptors, Interleukin / Q000032:analysis / Q000235:genetics; D053707:Receptors, Interleukin-12; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007071:Immunoglobulin A, Secretory; D015848:Interleukin-5; D010972:Platelet Activating Factor; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12; D017997:Leukotriene C4; D047209:Eosinophil Peroxidase