Interleukin-18: A Novel Cytokine That Augments Both Innate and Acquired Immunity

Okamura, Haruki; Tsutsui, Hiroko; Kashiwamura, Shin-ichiro; Yoshimoto, Tomohiro; Nakanishi, Kenji

doi:10.1016/s0065-2776(08)60389-2

Cited by 427 publications

(336 citation statements)

References 109 publications

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“…Whether a4b7 + leukocytes are involved in uNK cell differentiation is unclear, although cells of the monocyte/ macrophage lineage have been reported to play a key role as immunoregulatory cells at the maternal/fetal interface. Published data obtained from in situ hybridization studies suggest that macrophages present in the pregnant mouse uterus may be responsible for the production of IL-15 [22], and it has also been shown that macrophages are the major source of IL-12 and IL-18 in most tissues [23,24]. These cytokines were recently shown to be capable of activating NK cells [25,26], and King and co-workers described IL-15 receptor expression on human decidual NK cells [27].…”

Section: Discussionmentioning

confidence: 99%

Functional involvement of P‐selectin and MAdCAM‐1 in the recruitment of α4β7‐integrin‐expressing monocyte‐like cells to the pregnant mouse uterus

et al. 2004

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Leukocyte recruitment to the pregnant mouse uterus has been suggested to be associated with highly regulated expression of distinct patterns of vascular adhesion receptors. One of the most striking observations is the combined expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and P-selectin by maternal vessels of the vascular zone during the critical period of initial placenta development. The predominant cell population within these vessels is of the monocyte/macrophage lineage and expresses the mucosal integrin a4b7, which represents the ligand for MAdCAM-1; neutrophils and lymphocytes are rare. To directly assess the importance of identified adhesion receptors, we undertook longterm in vivo inhibition studies using monoclonal antibodies to inhibit the contribution of MAdCAM-1 in leukocyte trafficking to the decidua or to deplete a4b7 + leukocytes. In addition, implantation sites of mouse strains genetically deficient in specific adhesion receptors were investigated. Our results underline the importance of predicted adhesion pathways in the recruitment of monocyte-like cells, especially those expressing a4b7. Interestingly, maternal/ fetal units with inhibited recruitment of a4b7 + leukocytes or the absence of these cells are characterized by reduced size and frequency of uterine NK cells.

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Section: Discussionmentioning

confidence: 99%

Functional involvement of P‐selectin and MAdCAM‐1 in the recruitment of α4β7‐integrin‐expressing monocyte‐like cells to the pregnant mouse uterus

et al. 2004

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“…32,33 A central mediator of IL-12-induced responses is IFN-g, which is secreted upon IL-12 stimulation alone or with synergizing factors such as IL-2 and IL-18. 34,35 IFN-g, in turn, acts on APCs to initiate or increase IL-12 secretion in a positive feedback loop. 36 Apart from IFN-g release, IL-12 triggers the secretion of a number of other factors, including TNF-a, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-2.…”

Section: Il-12 Sensing By Innate and Adaptive Lymphocytesmentioning

confidence: 99%

New insights into IL-12-mediated tumor suppression

et al. 2014

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During the past two decades, interleukin-12 (IL-12) has emerged as one of the most potent cytokines in mediating antitumor activity in a variety of preclinical models. Through pleiotropic effects on different immune cells that form the tumor microenvironment, IL-12 establishes a link between innate and adaptive immunity that involves different immune effector cells and cytokines depending on the type of tumor or the affected tissue. The robust antitumor response exerted by IL-12, however, has not yet been successfully translated into the clinics. The majority of clinical trials involving treatment with IL-12 failed to show sustained antitumor responses and were associated to toxic side effects. Here we discuss the therapeutic effects of IL-12 from preclinical to clinical studies, and will highlight promising strategies to take advantage of the antitumor activity of IL-12 while limiting adverse effects.

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“…23 However, IL-18 is involved in both innate and acquired immunity during host defence against foreign pathogens and systemic neutralization could lead to severe impairment of the immune response. 24 Therefore, in some situations it appears preferable to choose local instead of systemic treatment. Studies by Bakker et al 25,26 already showed functionality of local intra-articular therapy for arthritis using IL-1 receptor antagonist.…”

Section: Introductionmentioning

confidence: 99%

Adenoviral delivery of IL-18 binding protein C ameliorates Collagen-Induced Arthritis in mice

Smeets¹,

Loo²,

Arntz³

et al. 2003

Gene Ther

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Interleukin-18: A Novel Cytokine That Augments Both Innate and Acquired Immunity

Cited by 427 publications

References 109 publications

Functional involvement of P‐selectin and MAdCAM‐1 in the recruitment of α4β7‐integrin‐expressing monocyte‐like cells to the pregnant mouse uterus

Functional involvement of P‐selectin and MAdCAM‐1 in the recruitment of α4β7‐integrin‐expressing monocyte‐like cells to the pregnant mouse uterus

New insights into IL-12-mediated tumor suppression

Adenoviral delivery of IL-18 binding protein C ameliorates Collagen-Induced Arthritis in mice

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