Interleukin-17 as a drug target in human disease

Ivanov, Stefan; Lindén, Anders

doi:10.1016/j.tips.2008.11.004

Cited by 98 publications

(117 citation statements)

References 102 publications

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“…In accordance with most of the studies on BAL and sputum samples, the results of this study suggest that IL-17A protein is moderately increased in patients with mild asthma, compared with healthy control subjects. It is of particular mechanistic interest that MATSUNAGA et al [42] obtained indications that the increase in IL-17A among these patients with asthma is associated with a corresponding increase in IL-8, tumour necrosis factor (TNF)-a and transforming growth factor (TGF)-b; cytokines that are associated with the mobilisation of neutrophils and Th17 cells [7][8][9][10][11][12][13]. It is also of mechanistic interest that MATSUNAGA et al [42] detected a trend towards a correlation between the concentration of ''exhaled'' IL-17A and airway obstruction in patients with asthma.…”

Section: Sputum Samplesmentioning

confidence: 99%

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Interleukin-17 cytokine signalling in patients with asthma

Lindén

Dahlén

2014

Eur Respir J

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Asthma remains a global health problem and, therefore, more effective pharmacotherapy is needed. This is particularly true for chronic and severe asthma. In these clinical phenotypes, chronic inflammation involving neutrophils is likely to play a pathogenic role, making it interesting to target cytokine signalling involved in the accumulation of neutrophils. Therefore, it is of interest that the archetype T-helper 17 cell cytokine interleukin (IL)-17A, perhaps also IL-17F, controls neutrophil accumulation, mucus secretion, macrophage mobilisation and smooth muscle reactivity in various experimental airway models. However, much less is known about the involvement of signalling via IL-17 cytokines in humans with asthma. Existing evidence suggests that these cytokines are released from several types of immune cells in asthma and, for IL-17A, there is a local increase associated with disease severity, with the mobilisation of neutrophils and smooth muscle cells locally in the airways. Even though the causative role of IL-17 cytokines remains unclear, there is potential for clinical utility in targeting IL-17A specifically in patients with moderate-to-severe asthma and high reversibility. There is a need for new and well-powered clinical investigations of signalling via IL-17 cytokines in this clinical phenotype. @ERSpublications There is potential utility for drugs targeting IL-17 cytokine signalling in a sub-group of patients with asthma

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Section: Sputum Samplesmentioning

confidence: 99%

“…The preceding work in various animal and cell models, including the experimental evidence from models of allergic asthma, has been extensively reviewed and presented previously [7][8][9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Interleukin-17 cytokine signalling in patients with asthma

Lindén

Dahlén

2014

Eur Respir J

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“…Secukinumab is a fully human monoclonal antibody that selectively neutralizes circulating IL-17a. Research suggests that IL-17a may play an important role in psoriasis, psoriatic arthritis and ankylosing spondylitis [1,2]. We have seen a case of psoriatic arthritis that was resistant to Anti-TNF therapy and successfully treated with Secukinumab.…”

Section: Introductionmentioning

confidence: 93%

Case Report of Secukinumabuse in Psoriatic Arthritis

Rk¹

2017

Austin J Orthopade & Rheumatol

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There are very few case reports of Secukinumab use in psoriatic arthritis. Most patients with psoriatic arthritis benefit from anti-TNF therapy but some do not respond, therefore unmet needs remain. Secukinumab is a fully human monoclonal antibody that selectively neutralizes circulating IL-17a. Research suggests that IL-17a may play an important role in psoriasis, psoriatic arthritis and ankylosing spondylitis [1,2]. We have seen a case of psoriatic arthritis that was resistant to Anti-TNF therapy and successfully treated with Secukinumab.

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“…3 Of note, ATRA has been already proven to be potentially useful for treatment of chronic hepatitis C, 4 but no data are not yet available for its use in ALD. An alternative approach might be represented by supplementation with essential omega-3 fatty acids, which have a demonstrated IL-17-decreasing effect 5 and whose potential usefulness to slow down liver injury has been already suggested. 6 Of interest is also the observation that some therapies currently used in ALD are also capable of acting on the IL-17 pathway.…”

Section: Interleukin-17-targeted Treatment Of Alcoholic Liver Diseasementioning

confidence: 99%

“…8 Additionally, anti-tumor necrosis factor-␣ therapy, which has been suggested for some patients with ALD, 7 can exert significant IL-17-decreasing effects. 5 In summary, the authors are to be congratulated for having performed an interesting study that might stimulate research in IL-17-targeted treatment of ALD. Hopefully this can ultimately improve the quality of life of these patients and, in some cases, even decrease shortterm mortality.…”

Section: Interleukin-17-targeted Treatment Of Alcoholic Liver Diseasementioning

confidence: 99%

Interleukin-17-targeted treatment of alcoholic liver disease

Emanuele

Bertona

2009

Hepatology

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Reply:We thank Drs. Manco and Nobili for reading our work and finding it interesting. Given the cross-sectional nature of the study we are unable to discern the sequence of metabolic events that might lead ultimately to insulin resistance and its complications. Due to the strong colinearity between visceral fat and intrahepatic fat accumulation, it is difficult to fully determine their relationship with glucose dysregulation, because both are strongly linked to gluconeogenesis. 1,2 Nevertheless, using multivariate analysis we found that hepatic fat content predicts the 2-hour plasma glucose independent of visceral fat (r 2 0.20, P Ͻ 0.04). Thus, hepatic fat content is a better predictor of prediabetes than visceral fat in obese adolescents.We agree that measurement of hepatic fat content could be a useful clinical tool to identify obese patients who are at increased risks for diabetes and cardiometabolic disease. Across a wide range of hepatic fat content, we found increasing worsening of insulin resistance, without an obvious threshold effect. Although hepatic insulin sensitivity was not directly measured in this study, other researchers have shown a monotonic increase in hepatic insulin resistance across varying degrees of hepatic steatosis. 2 Accurate assessment of hepatic fat content is essential in the clinical evaluation of the obese child presenting with cardiometabolic risks factors. Unfortunately, however, none of the available techniques are able to diagnose the presence of steatohepatitis and fibrosis, which can only be detected by liver biopsy. To the Editor:The recently published article by Korman et al. 1 suggests that the sequential use of two scores (alkaline phosphatase/total bilirubin ratio Ͻ 4 [94% sensitivity, 96% specificity] and aspartate aminotransferase/alanine aminotransferase ratio Ͼ 2.2 [94% sensitivity, 86% specificity]) in a population with acute liver failure can identify those with Wilson's disease with 100% sensitivity and 100% specificity. This is a statistical impossibility.Use of the first score will correctly identify 94% of patients with Wilson's disease and 96% of those without Wilson's disease. Applying the second score to the group with an alkaline phosphatase/total bilirubin ratio Ͻ 4 may improve the specificity, but the sensitivity (within the total population) cannot be greater than 94%. Applying the second score to that group with an alkaline phosphatase/total bilirubin ratio Ͼ 4 may improve the sensitivity, but the specificity (within the total population) cannot be greater than 86%. Applying the second score to both groups selected by the first score (i.e., the whole population) will result in 94% sensitivity and 86% specificity. DR. DAMIAN DOWLING

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Interleukin-17 as a drug target in human disease

Cited by 98 publications

References 102 publications

Interleukin-17 cytokine signalling in patients with asthma

Interleukin-17 cytokine signalling in patients with asthma

Case Report of Secukinumabuse in Psoriatic Arthritis

Interleukin-17-targeted treatment of alcoholic liver disease

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