Interleukin 9 promotes influx and local maturation of eosinophils.
The interleukin 9 (IL-9) pathway has recently been associated with the asthmatic phenotype including an eosinophilic tissue inflammation. The mechanism by which IL-9 affects eosinophils (eos) is not known. To investigate whether this cytokine has a direct activity on the development of eos and eosinophilic inflammation, a model of thioglycolate-induced peritoneal inflammation was used in IL-9 transgenic (TG5) and background strain (FVB) mice. In this model, a transient eosinophilic infiltration in the peritoneal cavity was observed in FVB mice 12 to 24 hours after thioglycolate injection that coincided with peak IL-5 and IL-9 release. In contrast, TG5 mice developed a massive eosinophilia that persisted at high levels (81% of total cells) even 72 hours after thioglycolate injection. Release of eosinophilic major basic protein (MBP), IL-4, and IL-5 to the peritoneal cavity of these mice was significantly increased when compared with the control FVB strain. To study the mechanism by which IL-9 exerts its effect on eos, bone marrow or peritoneal cells were cultured in the presence of IL-5, IL-9, or their combination in vitro. IL-5 alone was able to generate significant numbers of eos in TG5 but not FVB mice, whereas a combination of IL-5 and IL-9 induced marked eosinophilia in both strains indicating a synergism between these 2 cytokines. These data suggest that IL-9 may promote and sustain eosinophilic inflammation via IL-5-driven eos maturation of precursors.
Louahed
J
J
Magainin Institute of Molecular Medicine, Magainin Pharmaceuticals, Inc, Plymouth Meeting, PA, USA.
Zhou
Y
Y
Maloy
W L
WL
Rani
P U
PU
Weiss
C
C
Tomer
Y
Y
Vink
A
A
Renauld
J
J
Van Snick
J
J
Nicolaides
N C
NC
Levitt
R C
RC
Haczku
A
A
D019264:Adoptive Transfer; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D047091:Eosinophil Granule Proteins; D004802:Eosinophilia / Q000209:etiology*; D004804:Eosinophils / Q000187:drug effects*; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D016906:Interleukin-9 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008214:Lymphocytes / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018448:Models, Immunological; D020556:Neutrophil Infiltration / Q000187:drug effects; D010538:Peritonitis / Q000097:blood / Q000139:chemically induced* / Q000150:complications; D012260:Ribonucleases; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000637:transplantation; D013864:Thioglycolates / Q000633:toxicity; D013997:Time Factors
D001798:Blood Proteins; C515456:CCL11 protein, human; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D047091:Eosinophil Granule Proteins; D015848:Interleukin-5; D016906:Interleukin-9; D013864:Thioglycolates; D015847:Interleukin-4; D012260:Ribonucleases