Correlation between Proinflammatory Cytokines and Antiinflammatory Mediators and the Severity of Disease in Meningococcal Infections

Deuren, Marcel van; Ven-Jongekrijg, J. van der; Bartelink, A. K. M.; Dalen, R. van; Sauerwein, Robert W.; Meer, J.W.M. van der

doi:10.1093/infdis/172.2.433

Cited by 211 publications

(165 citation statements)

References 47 publications

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“…The finding of elevated pro-and anti-inflammatory cytokines in meningococcal disease demonstrated in this study confirm those previously published [1,2,13]. Unfortunately, due to limited plasma volumes available, we were unable to measure IL-10, which has previously been shown to be an important mediator.…”

Section: Discussionsupporting

confidence: 83%

“…These cytokines are produced principally by monocytes, macrophages and endothelial cells. The pro-inflammatory cytokines tumour necrosis factor-α (TNF), interleukin (IL) 1β, IL-6 and IL-8 increase rapidly, and their levels are correlated with severity of disease [1]. This is rapidly followed by a peak of anti-inflammatory cytokines IL-1 receptor antagonist (IL-1Ra), IL-10 and soluble TNF receptors (sTNFr) [2,3].…”

Section: Introductionmentioning

confidence: 99%

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A predominantly anti-inflammatory cytokine profile is associated with disease severity in meningococcal sepsis

et al. 2005

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Objective-This study aimed to determine whether an anti-inflammatory profile in meningococcal disease is associated with an increased risk of severe disease or septic shock.Design and setting-Prospective observational study in a tertiary care children's hospital. Patients and participants-63 children with confirmed meningococcal disease.Interventions-Plasma concentrations of interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-α (TNF) were assayed on admission. Receiver operator characteristic curve analysis was used to determine optimum thresholds for IL-1Ra:TNF, IL-1Ra:IL-6 and IL-1Ra:IL-8 ratios.Measurements and results-Median IL-1Ra:TNF and IL-1Ra:IL-6 ratios were significantly higher in severe disease with septic shock than in severe disease without septic shock and in non severe disease (IL-1Ra:TNF 263 vs. 185 vs. 108; IL-1Ra:IL-6 139 vs. 23 vs. 17). Median IL-1Ra:IL-8 ratios were not significantly different in the three groups. A significantly larger proportion of children with high IL-1Ra:TNF-α and IL-1Ra:IL-6 ratios developed severe disease with septic shock than those with a low ratios (95.2% vs. 4.8%; 76.2% vs. 23 .8%).Conclusions-An anti-inflammatory profile appears to be associated with the development of severe disease and septic shock in meningococcal sepsis. This may imply that experimental new therapies of pro-inflammatory cytokine inhibition and anti-inflammatory cytokines in meningococcal disease could be detrimental.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

A predominantly anti-inflammatory cytokine profile is associated with disease severity in meningococcal sepsis

et al. 2005

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“…Meningococcal meningitis is characterized by the presence of high levels of proinflammatory cytokines, including MC58 siaD + 1 mM SB202190 7.24 ± 2.9 1.18 ± 1.04 MC58 siaD + 10 mM SB202190 10.4 ± 4.9 1.33 ± 1.2 MC58 siaD + 20 mM SB202190 9.1 ± 5.7 1.28 ± 1.17 tumour necrosis factor-alpha (TNF-a), IL-1b, IL-6 and the CXC chemokine IL-8 (CXCL8) in the CSF (Waage et al, 1989;Ohga et al, 1994;van Deuren et al, 1995). A various number of bacterial surface components -in particular the lipooligosaccharide (LOS) -have been implicated in the release of cytokines induced by N. meningitidis in different cell types (Dixon et al, 2001;Kolb-Mäurer et al, 2001;Christodoulides et al, 2002;Unkmeir et al, 2002b).…”

Section: Activation Of P38 Mapk Is Implicated In N Meningitidisinducmentioning

confidence: 99%

Interaction of Neisseria meningitidis with human brain microvascular endothelial cells: role of MAP- and tyrosine kinases in invasion and inflammatory cytokine release

et al. 2004

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“…The joint pain experienced by these patients was possibly attributable to immune complex deposition or, perhaps, from the seeding of meningococci in the synovium or extra-articular connective tissue that causes pain without the typical clinical manifestation of joint inflammation. 4,28 Numerous studies have demonstrated increased serum concentrations of inflammatory mediators in patients with meningococcemia, 29,30 and these may play a role in the extremity pain experienced in patients with meningococcemia. It is known that interleukin-1 increases proteolysis in muscle without increasing muscle protein synthesis.…”

Section: Discussionmentioning

confidence: 99%

Extremity Pain and Refusal to Walk in Children With Invasive Meningococcal Disease

Inkelis

O’Leary²,

Wang

et al. 2002

Pediatrics

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ABSTRACT. Objective. Early recognition of invasive meningococcal disease in children may be difficult. Extremity pain and refusal to walk (extremity symptoms) are uncommonly mentioned as clinical findings in children who present with this disease. We sought to determine 1) the frequency of extremity symptoms as part of the clinical presentation in children with invasive meningococcal disease and 2) whether these symptoms help identify children with otherwise unsuspected meningococcal disease.Methods. We reviewed the medical records of patients who were younger than 20 years and had invasive meningococcal disease from 1985 to 1996 at 3 pediatric referral centers. Children with extremity symptoms were identified and described. We compared clinical and laboratory findings and frequency of adverse outcomes between these children and those with invasive meningococcal disease without extremity symptoms.Results. We identified 274 children with invasive meningococcal disease, 45 (16%) of whom had either history or physical examination evidence of extremity pain (31) or refusal to walk (14) as part of their clinical presentations. Five of the 45 patients had arthritis at the time of presentation. Patients with extremity symptoms at presentation were significantly older (77.9 ؎ 62.2 vs 44.0 ؎ 56.9 months), had lower temperatures (38.8 ؎ 1.2°C vs 39.2 ؎ 1.2°C), and had higher band counts (28.2 ؎ 15.2% vs 18.1 ؎ 12.4%) than did patients without extremity symptoms. There were no significant differences, however, between groups with regard to rash, white blood cell counts, coagulation parameters, prevalence of meningitis, or adverse outcomes. Seventy-three (27%) of the 274 patients had unsuspected disease, and 5 (7%) of these had extremity symptoms at the time of diagnosis.Conclusions. Sixteen percent of children with invasive meningococcal disease have extremity symptoms at the time of diagnosis. These symptoms may help to identify some patients with otherwise unsuspected invasive meningococcal disease. Pediatrics 2002;110(1). URL: http://www.pediatrics.org/cgi/content/full/110/1/e3; meningococcal infections, fever, bacteremia, myalgia, limp.ABREVIATIONS. CSF, cerebrospinal fluid; WBC, white blood cell; PT, prothrombin time; PTT, partial thromboplastin time; OR, odds ratio; CI, confidence interval; DIC, disseminated intravascular coagulation.T he clinical manifestations of invasive meningococcal disease in children typically consist of fever with toxic clinical appearance, irritability, lethargy, nuchal rigidity, hypotension, and petechial/purpuric rash. 1-6 Some children with invasive meningococcal disease, however, present in a more subtle manner with fever without clinical toxicity and other nonspecific symptoms, such as cough, rhinorrhea, vomiting, and headache, resembling an upper respiratory tract infection or other viral illness. [5][6][7] Although early recognition and treatment of meningococcal disease decreases complications, 7 neither the physical examination nor the hematologic evaluation reliably enables health ...

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Correlation between Proinflammatory Cytokines and Antiinflammatory Mediators and the Severity of Disease in Meningococcal Infections

Cited by 211 publications

References 47 publications

A predominantly anti-inflammatory cytokine profile is associated with disease severity in meningococcal sepsis

A predominantly anti-inflammatory cytokine profile is associated with disease severity in meningococcal sepsis

Interaction of Neisseria meningitidis with human brain microvascular endothelial cells: role of MAP- and tyrosine kinases in invasion and inflammatory cytokine release

Extremity Pain and Refusal to Walk in Children With Invasive Meningococcal Disease

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