Role of IL-18 in Acute Lung Inflammation

Jordan, Jacqueline A.; Guo, Renfeng; Yun, Edward C.; Sarma, Vidya; Warner, Roscoe L.; Crouch, Larry D.; Senaldi, Giorgio; Ulich, Thomas R.; Ward, Peter A.

doi:10.4049/jimmunol.167.12.7060

Cited by 95 publications

(78 citation statements)

References 50 publications

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“…Human IL-18BP also decreased IFN-␥ production and hepatic damage in mice after injection of Con A (20). The in vivo production of TNF-␣ and IL-1␤ by bronchoalveolar cells in immune complex-induced lung inflammation in rats also was decreased by intratracheal administration of IL-18BP (21). Thus, the exogenous administration of IL-18BP reduces the level of proinflammatory cytokines in different animal models of disease.…”

Section: Discussionmentioning

confidence: 76%

Mechanisms of Inhibition of Collagen-Induced Arthritis by Murine IL-18 Binding Protein

Banda

Vondracek

Kraus

et al. 2003

The Journal of Immunology

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130

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IL-18 is an important cytokine in autoimmune and inflammatory diseases through the induction of IFN-γ, TNF-α, and IL-1. We report herein that collagen-induced arthritis (CIA) in mice is inhibited by treatment with murine IL-18 binding protein (mIL-18BP). CIA was induced in DBA/1J mice by the injection of bovine type II collagen (CII) in IFA with added Mycobacterium tuberculosis on days 0 and 21. The mice were then treated for 3 wk with PBS or with two doses of mIL-18BP (0.5 and 3 mg/kg) as a fusion protein with the Fc portion of murine IgG1. Both the clinical disease activity scores and the histological scores of joint damage were reduced 50% in mice treated with either dose of mIL-18BP. Proliferation of CII-stimulated spleen and lymph node cells as well as the change in serum levels of IgG1 and IgG2a Ab to collagen between days 21 and 42 were decreased in mice treated with mIL-18BP. The production of IFN-γ, TNF-α, and IL-1β in cultured spleen cells was reduced by in vivo treatment with low dose, but not high dose, mIL-18BP. FACS analysis showed a slight decrease in NK cells and an increase in CD4+ T cells in spleens of mice treated with mIL-18BP. The steady state mRNA levels of IFN-γ, TNF-α, and IL-1β in isolated joints were all decreased in mice treated with both doses of mIL-18BP. The mechanisms of mIL-18BP inhibition of CIA include reductions in cell-mediated and humoral immunity to collagen as well as decreases in production of proinflammatory cytokines in the spleen and joints.

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Section: Discussionmentioning

confidence: 76%

Mechanisms of Inhibition of Collagen-Induced Arthritis by Murine IL-18 Binding Protein

Banda

Vondracek

Kraus

et al. 2003

The Journal of Immunology

Self Cite

130

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“…Moreover, we show that generation of such moieties may be subject to novel caspaseindependent processing pathways. IL-18 is a known enhancer of neutrophil effector function [20] that, when introduced into murine models, promotes neutrophilpredominated local inflammation [38,39]. In contrast, systemic inflammation following LPS injection is suppressed by anti-IL-18 antibodies, with concordant reduction in tissue neutrophil invasion to liver or lung [40].…”

Section: Discussionmentioning

confidence: 99%

Expression and alternative processing of IL‐18 inhuman neutrophils

et al. 2006

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Interleukin-18 (IL-18), a member of the IL-1 cytokine superfamily, is an important regulator of both innate and acquired immune responses. We demonstrate here constitutive expression of IL-18 by human neutrophils. Unexpectedly, we observed that neutrophils from peripheral blood or rheumatoid synovial compartments contained not only pro and mature IL-18, but also several novel smaller-molecular-weight IL-18-derived species. Using specific protease inhibitors, and serine protease gene-targeted mice, we demonstrate that these IL-18-derived products arose through caspaseindependent cleavage events mediated by the serine proteases, elastase and cathepsin G. Moreover, we report that the net effect of elastase treatment of mature recombinant IL-18 was to reduce its IFN-c-inducing activity. Thus, human neutrophils contain IL-18 and IL-18-derived molecular species that can arise through novel enzymatic processing pathways. Through cytosolic, membrane or secretory expression of such processing enzymes, together with generation of IL-18 itself, neutrophils likely play a critical role in regulating IL-18 activities during early innate immune responses.

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“…26 IL-18 is a known mediator of inflammation, with studies showing its role in many tissues including lung, heart, bowel, and cartilage. [27][28][29][30] IL-18 is activated by cleavage by caspase-1, and mice deficient in the enzyme are protected from AKI induced by IL-18 injection. 31 Further study showed the neutrophil-independent role that IL-18 has in ischemic AKI.…”

Section: Discussionmentioning

confidence: 99%

IL-18 and Urinary NGAL Predict Dialysis and Graft Recovery after Kidney Transplantation

Hall¹,

Yarlagadda²,

Coca³

et al. 2010

Journal of the American Society of Nephrology

288

218

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Current methods for predicting graft recovery after kidney transplantation are not reliable. We performed a prospective, multicenter, observational cohort study of deceased-donor kidney transplant patients to evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL), IL-18, and kidney injury molecule-1 (KIM-1) as biomarkers for predicting dialysis within 1 wk of transplant and subsequent graft recovery. We collected serial urine samples for 3 d after transplant and analyzed levels of these putative biomarkers. We classified graft recovery as delayed graft function (DGF), slow graft function (SGF), or immediate graft function (IGF). Of the 91 patients in the cohort, 34 had DGF, 33 had SGF, and 24 had IGF. Median NGAL and IL-18 levels, but not KIM-1 levels, were statistically different among these three groups at all time points. ROC curve analysis suggested that the abilities of NGAL or IL-18 to predict dialysis within 1 wk were moderately accurate when measured on the first postoperative day, whereas the fall in serum creatinine (Scr) was not predictive. In multivariate analysis, elevated levels of NGAL or IL-18 predicted the need for dialysis after adjusting for recipient and donor age, cold ischemia time, urine output, and Scr. NGAL and IL-18 quantiles also predicted graft recovery up to 3 mo later. In summary, urinary NGAL and IL-18 are early, noninvasive, accurate predictors of both the need for dialysis within the first week of kidney transplantation and 3-mo recovery of graft function.

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Role of IL-18 in Acute Lung Inflammation

Cited by 95 publications

References 50 publications

Mechanisms of Inhibition of Collagen-Induced Arthritis by Murine IL-18 Binding Protein

Mechanisms of Inhibition of Collagen-Induced Arthritis by Murine IL-18 Binding Protein

Expression and alternative processing of IL‐18 inhuman neutrophils

IL-18 and Urinary NGAL Predict Dialysis and Graft Recovery after Kidney Transplantation

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