Interleukin-18 stimulates hematopoietic cytokine and growth factor formation and augments circulating granulocytes in mice.
Because interleukin-18 (IL-18) is similar to IL-1 and is known to be involved in the hematopoietic progenitor cell growth, the effect of IL-18 on circulating cell populations was examined. Repeated administration of IL-18 induced significant amounts of neutrophilia in mice. In parallel, high levels of interferon-gamma (IFN-gamma), IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were detected in the serum of these mice. Interestingly, the cytokine profiles as well as the cell populations in circulation altered around 2 weeks after the beginning of IL-18 administration. A weak but definite eosinophilia was observed concurrently with the appearance of serum IL-5. Consistent with these observations, IL-18 induced secretion of IFN-gamma, GM-CSF, and IL-6 from splenocytes in culture. IL-18 also induced low levels of IL-5 in the splenocyte culture, which was inhibited by IL-12. However, markedly high levels of IL-5 were secreted into the culture medium when splenocytes from IFN-gamma-deficient mice were stimulated by IL-18. CD4(+) T cells strongly responded to IL-18 to secrete IL-5 and GM-CSF. IL-18 stimulated secretion of IL-6 and expression of G-CSF mRNA in splenic adherent cells. Expression of IL-18 receptors was detected in CD4(+) T cells and splenic adherent cells (macrophages). These results show that IL-18 stimulates CD4(+) T cells and macrophages to secrete IL-5, GM-CSF, IL-6, and granulocyte-colony stimulating factor in the absence of IL-12, which in turn induces hematopoietic cell proliferation causing neutrophilia and eosinophilia in mice.
Ogura
T
T
Biochemistry II group, Research Department, Sawai Pharmaceutical, Osaka, Japan.
Ueda
H
H
Hosohara
K
K
Tsuji
R
R
Nagata
Y
Y
Kashiwamura
S
S
Okamura
H
H
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects*; D016298:Hematopoietic Cell Growth Factors / Q000096:biosynthesis* / Q000187:drug effects*; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology; D020382:Interleukin-18 / Q000008:administration & dosage / Q000494:pharmacology*; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D020382:Interleukin-18; D007371:Interferon-gamma