Selected CC and CXC chemokines in children with atopic asthma

Abstract

IntroductionThere are only limited data on CC and CXC chemokines regulation in children with asthma.AimWe compared the serum profile of selected CC and CXC chemokines in patients with atopic asthma and healthy children.Material and methodsSerum concentration of CC chemokines RANTES, MCP-1, and CXC chemokines IP-10, MIG, IL-8, RANTES was measured using cytometric bead array in 44 children with atopic asthma and 17 healthy subjects.ResultsThe concentration of RANTES was significantly higher and the MIG level was lower in all children with asthma as compared to their control counterparts. We observed increased RANTES and decreased MIG levels also in patients with stable asthma when compared with children in the control group. The IP-10 concentration was similar between the whole asthma group and healthy controls, while significantly increased levels of this chemokine in acute asthma have been observed when compared to stable asthma. For MCP-1 and IL-8, the serum concentration was similar in all compared groups. The MIG concentration correlated positively with IP-10, IL-8, and CRP levels and negatively with the eosinophil count. A negative correlation between the IP-10 and eosinophil count and a negative correlation between FEV1 and IP-10 were found.ConclusionsAn increased serum RANTES level in children with asthma may result in enhancement of Th2 lymphocyte recruitment into the airway. A decreased expression of Th1 chemokine MIG in children with stable asthma may contribute to a diminished antagonizing effect on Th2 cytokine production and hence intensify Th2 predominance. An increased IP-10 level in children during an asthma attack suggest that this chemokine is a serological marker of disease exacerbation.

Severe asthma in humans and mouse model suggests a CXCL10 signature underlies corticosteroid-resistant Th1 bias

“…Having observed increased expression of CXCL10 in the BAL cells of a subset of severe asthmatics correlating strongly with IFNG expression, and given the utility of monocytes to study mechanisms of CXCL10 gene expression, we used the human monocytic cell line THP-1 as well as peripheral blood monocytes to assess CXCL10 mRNA and protein expression in the context of IFN-γ and CS. Given elevations of CXCL10 levels in type 2-associated inflammatory states in mouse models of asthma (26,27), as well as in mild-moderate atopic asthma as described above (17,21,23), we hypothesized that IFN-γ-mediated induction of CXCL10 might be uniquely insensitive to CS compared with when it is induced by other stimuli. LPS is also a well-studied inducer of CXCL10, but there are differences in CXCL10 promoter utilization between IFN-γ and LPS (14).…”

“…Most prior studies of CXCL10 in asthma have focused on atopic and mild disease (17,21,23). Interestingly, CXCL10 protein level was found to increase significantly upon segmental allergen challenge in humans (20).…”

“…In addition to its expression on Th1 cells, the CXCR3 receptorwhich mediates chemoattraction by CXCL10 and its family members -is also present on mast cells (17), neutrophils (18), and eosinophils (19). Elevated CXCL10 levels have been detected in multiple compartments, including blood and bronchoalveolar lavage (BAL) in mild and atopic asthma (20)(21)(22) and may be increased during asthma exacerbations (23). CXCL10 can be secreted by multiple cell types, including airway epithelial cells, smooth muscle cells, monocytes, and macrophages (11).…”

Protein Biomarkers in Asthma

“…In addition, increased serum RANTES levels in children with atopic asthma in comparison with healthy children have been observed [76]. Moreover, children with unstable asthma have significantly higher RANTES levels in inhaled breath condensate.…”

“…IP-10 is a predominant chemokine measured during human allergic pulmonary latephase reactions. A significant increase in serum levels of IP-10 during an asthma attack in children [76] and in patients with occupational asthma [82] in contrast to healthy controls suggests that IP-10 is a serological marker of exacerbation. Moreover, IP-10 values can be useful for discrimination of acute exacerbations in patients with virus-induced asthma, as serum IP-10 levels were significantly higher in non-sensitized patients [83].…”