Interleukin-10 regulation in normal subjects and patients with asthma

Borish, Larry; Aarons, Alan; Rumbyrt, Jeffrey; Cvietusa, Peter; Negri, Julie; Wenzel, Sally E.

doi:10.1016/s0091-6749(96)70197-5

Cited by 445 publications

(311 citation statements)

References 42 publications

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“…Those responses were consistent with what would be expected with a lack of IL-10 as an anti-inflammatory cytokine and are in agreement with phenotypic expectations that would come from human data demonstrating a lack of IL-10 production in asthmatics (7,8). However, it must be acknowledged that those results were obtained with a stronger OVA stimulus (five higher concentration OVA challenges), which may have profound effects on the induction of AI and the subsequent measures of cell recruitment, cytokines, NO production, and airway responsiveness (42).…”

Section: Critique Of Methodssupporting

confidence: 90%

“…The production of IL-10 in this manner constitutes a negative feedback loop that down-regulates TNF-␣ (5) and promotes resolution of the inflammatory response (6). However, IL-10 production by airway immune cells of asthmatics has been shown to be reduced (7,8), which has led to postulation that lack of this antiinflammatory cytokine may allow allergic proinflammatory mechanisms to dominate, which in turn, may promote development of asthma and possibly airway remodeling.…”

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confidence: 99%

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Alterations in Nitric Oxide and Cytokine Production with Airway Inflammation in the Absence of IL-10

Ameredes

Zamora

Sethi

et al. 2005

The Journal of Immunology

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IL-10 is an anti-inflammatory cytokine that suppresses NO synthase (NOS) and production of NO; its lack may promote NO production and alterations in cytokines modulated by NO with allergic airway inflammation (AI), such as IL-18 and IL-4. Therefore, we induced AI in IL-10 knockout (−/−) and IL-10-sufficient C57BL/6 (C57) mice with inhaled OVA and measured airway NO production, as exhaled NO (ENO) and bronchoalveolar lavage fluid nitrite levels. ENO and nitrite levels were elevated significantly in naive IL-10−/− mice as compared with C57 mice. With AI, ENO and nitrite levels increased in C57 mice and decreased in IL-10−/− mice. IL-18 production fell with both AI and addition of S-nitroso-N-acetyl-d,l-penicillamine (a NO donor) but was not significantly increased by chemical NOS inhibition by l-N5-(1-iminoethyl)-ornithine. IL-4 AI was increased significantly (up to 10-fold greater) in the absence of IL-10 but was reduced significantly with chemical inhibition of NOS. Airway responsiveness was lower in IL-10−/− mice and was associated with alteration in production of NO and IL-4. Thus, IL-4 production was increased, and likely decreased NO production, in a way not predicted by the absence of IL-10. Inhibition of IL-4 production, with inhibition of NOS in the absence of IL-10, demonstrated the importance of a NO and IL-4 feedback mechanism regulating this interaction.

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Section: Critique Of Methodssupporting

confidence: 90%

mentioning

confidence: 99%

Alterations in Nitric Oxide and Cytokine Production with Airway Inflammation in the Absence of IL-10

Ameredes

Zamora

Sethi

et al. 2005

The Journal of Immunology

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“…IL-10 is produced by cells of individuals chronically infected with S. mansoni and there are some S. mansoni antigens able to induce IL-10 production in vitro. On the other hand, there is impaired production of IL-10 in asthmatic individuals, even when their cells are stimulated in vitro with dust mite antigens (Araujo et al 2004) and LPS (Borish et al 1996, Tomita et al 2002. In this study we evaluated the ability of some schistosome vaccine candidate antigens, ie, Sm14, Sm 22.6, p24, and PIII in induce IL-10 production by cells from asthmatic infected individuals.…”

Section: Discussionmentioning

confidence: 99%

Schistosoma mansoni antigen-driven interleukin-10 production in infected asthmatic individuals

Cardoso

Oliveira

Pacífico

et al. 2006

Mem. Inst. Oswaldo Cruz

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Asthmatics infected with Schistosoma mansoni have a less severe course of asthma and an inhibition of the Th2 inflammatory response that seems to be mediated by interleukin . The objective of this study was to evaluate the capacity of some S. mansoni antigens to stimulate IL-10 production in vitro by cells of asthmatic infected individuals. Peripheral bloods mononuclear cells were stimulated with the S. mansoni recombinant antigens Sm22.6, Sm14, P24, was measured in the supernatants of cultures. As the recombinant antigens were cloned in Escherichia coli, we blocked contaminant endotoxin with polymyxin B added to the cultures. We demonstrated that all antigens used drove high production of IL-10 in S. mansoni infected individuals (n = 13, 408 ± 514 and 401 ± 383 pg/ml, 484 ± 245 pg/ml, 579 ± 468 pg/ml, respectively). In asthmatics infected with S. mansoni (n = 21) rP24 induced higher levels of rSm14 and rSm22.6 (184 ± 209 pg/ml; 292 ± 243 pg/ml; 156 ± 247 pg/ml, respectively). Conclusion: the S. mansoni antigens evaluated in this study stimulated IL-10 production by cells from infected individuals and therefore they have the potential to be used as a modulator of the inflammatory response in asthma. Key words: Schistosoma mansoni recombinant proteins -S. mansoni antigens -interleukin-10Evidences has accumulated that helminth infections protect against the development of allergy. For instance Lynch et al. (1993) demonstrated an inhibition of the skin prick test response to aeroallergens in individuals infected with Ascaris lumbricoides, and that the anti-helminthic treatment resulted in an increase in the prevalence of positive skin tests. These findings were supported by others authors (van den Biggelaar et al. 2000) and in the last few years some studies have demonstrated that Schistosoma mansoni infection not only suppresses the skin prick test response, but modulates asthma severity (Araujo et al. 2000, van den Biggelaar et al. 2000, Medeiros et al. 2003.Asthma is a multifatorial disease that results from genetic predisposition, exposure to allergens and environmental factors. While some environmental factors precipitate the development of asthma, others seem to be protective. This is the case of helminth infections, particularly S. mansoni, which through the modulation of the inflammatory response prevent asthma (Medeiros et al. 2003, Araujo et al. 2004. Studying the mechanisms behind the protection against allergy, Araujo et al. (2004) found that interleukin (IL-10) seems to play an important role in modulating the Th2 inflammatory response involved in the pathology of allergic diseases. Supporting this idea, Bigellar et al. showed high levels of this cytokine in individuals infected with S. haematobium who did not respond to skin test to aeroallergens (van den Biggelaar et al. 2000).It is well known that the acute phase of S. mansoni infection is characterized by a strong Th1 inflammatory response that evolues to a parasite antigen-driven Th2 response cronically . It is also known that this down modula...

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“…IL10 reduces IL4 and IL5 expression as well as IgE titers and eosinophil rates [Moore et al, 1993;van Scott et al, 2000]. Its expression is significantly reduced in asthmatics [Borish et al, 1996], which may be partly due to the IL10-592A SNP in the promoter re-gion [Rosenwasser and Borish, 1997]. Nitric oxide (NO) is an important intercellular transmitter playing a key role in the bronchomotoric control in the lungs of mammals [Grasemann et al, 1999].…”

Section: Introductionmentioning

confidence: 99%

Fine mapping and single nucleotide polymorphism association results of candidate genes for asthma and related phenotypes

et al. 2001

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Several genome-wide screens for asthma and related phenotypes have been published to date but data on fine-mapping are scarce. For higher resolution we performed a fine-mapping study with 2 cM average spacing in often discussed asthma candidate regions (2p, 5q, 6p, 7p, 9q, 11p, and 12q) to narrow down the regions of interest. All participants of a Caucasian family study (97 families with at least two affected sib pairs) were genotyped for 49 supplementary polymorphic dinucleotide markers. Our results indicate increased evidence for linkage on chromosome 6p, 9q, and 12q. These candidate regions were further analyzed with SNP polymorphisms in the endothelin 1 (EDN1), lymphotoxin alpha (LTA), and neuronal nitric oxide synthase (NOS1) genes. In addition, IL4 -590C>T and IL10 -592C>A, localized on chromosomes 5q and 1q, respectively, have been analyzed for SNP association. Of the six SNPs tested, four revealed weak association with the examined phenotypes. These are the IL10 -592C>A SNP in the interleukin 10 gene (p=0.036 for eosinophil cell counts), the 4124T>C SNP in EDN1 (p=0.044 for asthma), the 3391C>T SNP in NOS1 with eosinophil cell counts (p=0.0086), and the 5266C>T polymorphism, also in the NOS1 gene, for high IgE levels (p=0.022). In summary, fine mapping data enable us to confine asthma candidate regions, while variants of EDN1 and NOS1, or nearby genes, may play an important role in this context. Hum Mutat 18:327 336, 2001.

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Interleukin-10 regulation in normal subjects and patients with asthma

Cited by 445 publications

References 42 publications

Alterations in Nitric Oxide and Cytokine Production with Airway Inflammation in the Absence of IL-10

Alterations in Nitric Oxide and Cytokine Production with Airway Inflammation in the Absence of IL-10

Schistosoma mansoni antigen-driven interleukin-10 production in infected asthmatic individuals

Fine mapping and single nucleotide polymorphism association results of candidate genes for asthma and related phenotypes

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