Intracerebroventricular interleukin-6, macrophage inflammatory protein-1β and IL-18: pyrogenic and PGE2-mediated?

Li, Shuxin; Goorha, Salil; Ballou, Leslie R.; Blatteis, Clark M.

doi:10.1016/j.brainres.2003.08.033

Cited by 61 publications

(40 citation statements)

References 44 publications

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“…Discussion IL-1␤, IL-18, COX-2, and Fever. The present study was performed to examine the differences between IL-1␤ and IL-18 for the induction of COX-2, because injection of IL-18 does not cause fever in animals (5,17,18). These data are in sharp contrast to the ability of IL-1 to produce fever in animals and humans at exceedingly low doses of a few nanograms per kilogram (13).…”

Section: Cox-2 Protein and Pge2 Levels After Il-18mentioning

confidence: 96%

“…In subjects with genetic defects in caspase-1 activity resulting in spontaneous secretion of IL-1␤, there is a prompt reduction in fever after a single injection of IL-1Ra (24,25). IL-1-induced fever depends on COX-2 and not COX-1-induced PGE 2 (3)(4)(5). In human synovial cells, half-maximal stimulation of PGE 2 by IL-1␤ is achieved at 1.3 Ϯ 0.24 pM (18-27 pg͞ml) (26).…”

Section: Cox-2 Protein and Pge2 Levels After Il-18mentioning

confidence: 99%

“…Therefore, the failure of IL-18 to induce fever is linked to COX-2. Although one could argue that the lack of IL-18 receptors on the specialized endothelial cells of the hypothalamic thermoregulatory center explains the lack of fever, direct injection of IL-18 into the brain also does not evoke a febrile response (5). Moreover, there is not a dearth of evidence that the brain is highly responsive to endogenous as well as exogenous IL-18 (18,27), and that the brain expresses IL-18 receptors (28)(29)(30).…”

Section: Cox-2 Protein and Pge2 Levels After Il-18mentioning

confidence: 99%

“…COX-2, however, is inducible by proinflammatory stimuli, particularly the cytokine IL-1 (2). COX-2-deficient mice, for example, do not develop fever to endotoxin (3), IL-1␤ (4), or IL-6 (5), whereas COX-1-deficient mice do exhibit fever after systemic or intracerbroventricular injections of these pyrogens (3)(4)(5). In addition to fever, the importance of PG E 2 (PGE 2 ) is best appreciated in malignant transformation in patients at high risk for developing malignant adenomas of the intestinal tract.…”

mentioning

confidence: 99%

“…Although IL-18 has been reported to induce COX-2 gene expression in the articular chondrocytes (16), IL-18 does not cause fever (5,17,18), which depends on COX-2 (3,4). Humans, who are highly responsive to the rapid pyrogenic response of i.v.…”

mentioning

confidence: 99%

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Differences in signaling pathways by IL-1β and IL-18

Lee

Kim

Lewis

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

220

148

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Section: Cox-2 Protein and Pge2 Levels After Il-18mentioning

confidence: 96%

Section: Cox-2 Protein and Pge2 Levels After Il-18mentioning

confidence: 99%

Section: Cox-2 Protein and Pge2 Levels After Il-18mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Differences in signaling pathways by IL-1β and IL-18

Lee

Kim

Lewis

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

220

148

View full text Add to dashboard Cite

IL-1 Superfamily and Inflammasome

Dinarello

2017

Inflammation - From Molecular and Cellular Mechanisms to the Clinic

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Rapid responses to anakinra in patients with refractory adult‐onset Still's disease

Fitzgerald

LeClercq

Yan

et al. 2005

Arthritis & Rheumatism

334

159

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Objective. To assess the efficacy of anakinra treatment in patients with adult-onset Still's disease (AOSD) that is refractory to corticosteroids, methotrexate (MTX), and etanercept.Methods. Four patients with AOSD were treated with prednisone and MTX and 2 patients were also treated with etanercept for worsening symptoms and indicators of systemic inflammation. White blood cells (WBCs), C-reactive protein (CRP) levels and/or erythrocyte sedimentation rate, and ferritin levels were measured and, in 1 patient, serum creatinine levels were determined. Treatment with anakinra at 100 mg/day was initiated.Results. The index patient's disease was refractory to treatment with prednisone (30 mg/day) and MTX, with spiking fevers, rash, synovitis, a serum ferritin level of 8,400 ng/ml (normal <200), and a CRP level of 86 mg/liter (normal <8). Levels of interleukin-1␤ (IL-1␤), IL-1␣, IL-6, IL-1 receptor antagonist, and IL-18 were elevated. Just prior to anakinra treatment, the WBC count was 14,600/mm 3 , the CRP level was 86 mg/liter, and the ferritin level was 573 ng/ml, with daily spiking fevers to 104°F, rash, and swollen joints. Within hours of the first injection, the patient was afebrile and asymptomatic; within days, the WBC count, ferritin level, and CRP level decreased into the normal range.On 2 occasions, anakinra was withheld. Within a few days, the WBC count rose to >20,000/mm 3 with prominent neutrophilia, the CRP level rose to >200 mg/liter, and the ferritin level rose to >3,000 ng/ml. Upon restarting anakinra, the patient became afebrile, the WBC count fell to 8,000/mm 3 , the CRP level fell to <3 mg/liter, and the ferritin level fell to <300 ng/ml. Three additional patients with refractory AOSD who experienced rapid reductions in fever, symptoms, and markers of inflammation when treated with anakinra are reported.Conclusion. Refractory AOSD appears to be IL-1-mediated since anakinra decreases hematologic, biochemical, and cytokine markers and also produces rapid reductions in systemic and local inflammation. Reported efficacy of tumor necrosis factor-blocking therapies in AOSD may be due to a reduction in IL-1.Adult-onset Still's disease (AOSD), a rheumatologic condition found worldwide, is characterized by a variety of clinical features, including intermittent fever, arthritis, evanescent rash, sore throat, leukocytosis, and hepatic dysfunction, polyserositis, lymphadenopathy, splenomegaly, and other systemic symptoms. Because of the diverse presentation (1), classifications have been developed to standardize the diagnosis of AOSD. The most widely accepted criteria set, as presented by Yamaguchi and colleagues (2), is a compilation of major and minor criteria with the exclusion of infections, malignancies, and other rheumatic or systemic diseases. More recently, Fautrel and associates have proposed classification criteria utilizing diagnostic markers of serum ferritin and glycosylated ferritin, thought to be more specific for AOSD (3). These criteria are said to provide a sensitivity of 80.6% and a specifi...

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Intracerebroventricular interleukin-6, macrophage inflammatory protein-1β and IL-18: pyrogenic and PGE2-mediated?

Cited by 61 publications

References 44 publications

Differences in signaling pathways by IL-1β and IL-18

Differences in signaling pathways by IL-1β and IL-18

IL-1 Superfamily and Inflammasome

Rapid responses to anakinra in patients with refractory adult‐onset Still's disease

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