TNF? Archives - World Asthma Foundation

Anti-inflammatory activity of IL-37 in asthmatic children: Correlation with inflammatory cytokines TNF-?, IL-?, IL-6 and IL-17A.

Immunobiology. 2015 Sep 8;

Authors: Charrad R, Berraïes A, Hamdi B, Ammar J, Hamzaoui K, Hamzaoui A

Abstract
BACKGROUND: The aim of this study was to assess interleukin (IL)-37 production in asthmatic children in serum and induced sputum and to look to the impact of IL-37 on pro-inflammatory cytokines production (TNF-?, IL-6, IL-1? and IL-17).
METHODS: Forty children with well-controlled asthma (20 moderate and 20 mild asthmatics) were studied. IL-37 was measured by ELISA in serum and induced sputum (IS) samples, and compared with 22 age- and sex-matched healthy controls. Real-time quantitative PCR was used to determine IL-37 mRNA expression in induced sputum cells. Induced sputum mononuclear cells from 10 moderate asthmatics and 10 healthy controls were stimulated either with lipopolysaccharides (LPS) or LPS plus recombinant IL-37 (rIL-37) comparing pro-inflammatory cytokines production. TNF-?, IL-1?, IL-6 and IL-17 were measured by RT-PCR and ELISA.
FINDINGS: The expression of IL-37 mRNA in asthmatic patients was significantly lower than that observed in healthy controls (P=0.0001). IL37 mRNA expression depended on asthma severity. Serum and IS IL-37 levels were significantly lower in asthma patients compared to healthy controls. LPS-stimulated sputum cells from asthma patients produced higher levels of IL-1?, IL-6, and TNF-? than those from HC. Adding rIL-37 suppressed TNF-?, IL-1? and IL-6 production in IS cells. In the same way, stimulating IS CD4(+) T cells in the presence of rIL-37 inhibited IL-17 production both in asthma patients and HC. IL-37 effect on IL-17 was more pronounced in patients than controls.
INTERPRETATION: The decrease in IL-37 level observed in IS was found to correlate with disease severity. The increased pro-inflammatory cytokines production from asthma IS cells was abrogated by the addition of rIL-37. IL-37 could be an important cytokine in the control of asthma by suppressing the production of inflammatory cytokines.

PMID: 26454413 [PubMed – as supplied by publisher]

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Alveolar Macrophages Play a Key Role in Cockroach-Induced Allergic Inflammation via TNF-? Pathway.

PLoS One. 2012;7(10):e47971

Authors: Kim JY, Sohn JH, Choi JM, Lee JH, Hong CS, Lee JS, Park JW

Abstract
The activity of the serine protease in the German cockroach allergen is important to the development of allergic disease. The protease-activated receptor (PAR)-2, which is expressed in numerous cell types in lung tissue, is known to mediate the cellular events caused by inhaled serine protease. Alveolar macrophages express PAR-2 and produce considerable amounts of tumor necrosis factor (TNF)-?. We determined whether the serine protease in German cockroach extract (GCE) enhances TNF-? production by alveolar macrophages through the PAR-2 pathway and whether the TNF-? production affects GCE-induced pulmonary inflammation. Effects of GCE on alveolar macrophages and TNF-? production were evaluated using in vitro MH-S and RAW264.6 cells and in vivo GCE-induced asthma models of BALB/c mice. GCE contained a large amount of serine protease. In the MH-S and RAW264.7 cells, GCE activated PAR-2 and thereby produced TNF-?. In the GCE-induced asthma model, intranasal administration of GCE increased airway hyperresponsiveness (AHR), inflammatory cell infiltration, productions of serum immunoglobulin E, interleukin (IL)-5, IL-13 and TNF-? production in alveolar macrophages. Blockade of serine proteases prevented the development of GCE induced allergic pathologies. TNF-? blockade also prevented the development of such asthma-like lesions. Depletion of alveolar macrophages reduced AHR and intracellular TNF-? level in pulmonary cell populations in the GCE-induced asthma model. These results suggest that serine protease from GCE affects asthma through an alveolar macrophage and TNF-? dependent manner, reflecting the close relation of innate and adaptive immune response in allergic asthma model.

PMID: 23094102 [PubMed – in process]

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