Increased serum IL‐10/IL‐12 ratio in wheezing infants

Koopman, Laurens P.; Savelkoul, H.F.J.; Benten, I.J. van; Gerritsen, Jorrit; Brunekreef, Bert; Neijens, H. J.

doi:10.1034/j.1399-3038.2003.00019.x

Cited by 13 publications

(13 citation statements)

References 38 publications

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“…The association of serum sICAM-1 with persistent wheezing indicates airway inflammation. Infant serum sICAM-1 predicted the onset of wheezing in the second year of life (30). Together our results suggest that different inflammatory processes separate persistent from transient wheezers early in life.…”

Section: Discussionsupporting

confidence: 54%

Bronchoalveolar Lavage MMP-9 and TIMP-1 in Preschool Wheezers and Their Relationship to Persistent Wheeze

et al. 2008

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Atopic preschool children are more likely to develop persistent wheezing, which could be a consequence of early airway remodeling. Protease-antiprotease balance between MMP-9 and its cognate inhibitor TIMP-1 may be involved in this process. Our hypothesis was that atopic wheezing preschool children would have an imbalance of MMP-9 to TIMP-1 in bronchoalveolar lavage (BAL). BAL from 52 preschool wheezers was compared with 14 controls without wheeze. A subgroup completed an International Study of Asthma and Allergy in Childhood symptom questionnaire 2 y later. Molar ratios of MMP-9/TIMP-1 were higher in wheezy children (p Ͻ 0.001; median 4.0%, range 0 -8.7) than controls (0.6%, 0 -1.8), and showed an excess of TIMP-1 in the airway. BAL TIMP-1 was raised in children with persistent wheezing (p ϭ 0.028; 34.4 ng/mL, 9.1-93.1 compared with 10.6 ng/mL 6.1-18.6), as was serum levels of intercellular adhesion molecule-1 (p ϭ 0.027). The absolute concentration of TIMP-1 in the airway, rather than its molar ratio with MMP-9, was associated with persistent wheezing. The processes involved with airway remodeling are complex but excess TIMP-1 may impede matrix protein turnover and thereby contribute to persistent changes in airway structure and wheezing. W heezing is a common respiratory symptom among preschool children and while most outgrow their disease by mid childhood, some continue to wheeze and develop asthma. Atopic preschool children are more likely to have persistent wheezing associated with progressively reducing pulmonary function (1). The cause of this deteriorating pulmonary function is not known, but airway remodeling is implicated in the disease process, and has been found in school-aged children with asthma (2-6). Thickening of the epithelial basement membrane (EBM) is an age related event detectable by 3 y of age in severe recurrent wheezers (7,8).Although the inflammatory mechanisms underlying the remodeling process are not known, protease anti-protease balance is one factor that could lead to a disorder of matrix turnover (9). The matrixins are a family of proteases able to digest components of the extracellular matrix (ECM). Matrix metalloproteinase 9 (MMP-9) is the predominant matrixin in pulmonary tissue and is specifically inhibited by tissue inhibitor of metalloproteinase-1 (TIMP-1) in a 1:1 ratio (10). There are two opposing mechanisms by which MMP-9 and TIMP-1 could affect a remodeling process: First, an excess of active MMP-9 over TIMP-1 would allow unregulated destruction of the ECM leading to inflammation and wound repair (11). Second, an excess of TIMP-1 over MMP-9 would slow the turnover of the ECM, which may include thickening of the EBM.Although, there is accumulating evidence of a role for MMP-9 and TIMP-1 in adult asthma (11-16), there are conflicting results in children, in an age group where structural remodeling may actually be occurring (17,18). The aim of this study was to investigate MMP-9 and TIMP-1 in bronchoalveolar lavage (BAL) from preschool wheezers. Our hypotheses wer...

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Section: Discussionsupporting

confidence: 54%

Bronchoalveolar Lavage MMP-9 and TIMP-1 in Preschool Wheezers and Their Relationship to Persistent Wheeze

et al. 2008

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“…This could, in part, contribute to the frequent recurrence of URTI. On the other hand, IL-10 production was found to be associated in infants with increased risk of development of recurrent wheezing (26,27). Although several studies have demonstrated that reduced IFN-␥ levels are a marker for higher risk of allergy (28), our patients did not show allergic symptoms despite of the reduced IFN-␥ levels.…”

Section: Adhesion Molecules and Cytokines In Urtimentioning

confidence: 36%

Soluble Adhesion Molecules and Cytokines in Children Affected by Recurrent Infections of the Upper Respiratory Tract

et al. 2004

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The objective of this study was to compare plasma levels of soluble adhesion molecules and Th1-Th2 type cytokines in 44 children with frequently recurrent respiratory infections (FRRI) of upper airways, defined as having nine or more episodes per year, and in 34 children without recurrence; all subjects were followed-up for 12 mo. The viral etiology was determined by cultures from nasal, pharyngeal, and ear secretions, using PCR and immunofluorescence. Plasma levels of five soluble adhesion molecules (E-selectin, P-selectin, L-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1) and interferon (IFN)-␥, IL-12, IL-4, and IL-10 were measured in patients and in 15 healthy controls using sandwich ELISA. During acute phase, all patients showed significant increase in plasma levels of soluble adhesion molecules; during the followup, the levels were greater in children with FRRI. A difference of cytokine profile was demonstrated between the patients with and without FRRI: an increased IL-4 and IL-10 release with decreased levels of IFN-␥ and IL-12 suggested a skewing into Th2-type response, in patients with FRRI. This pattern persisted during the follow-up. In patients without recurrence, an increased IFN-␥ and IL-12 release, together with decreased levels of IL-4 and IL-10, showed a skewing into Th1-type responses; in the follow-up these cytokines reached normal values. In conclusion, the abnormal levels of all examined parameters in children with FRRI may reflect the persistence of an inflammatory microenvironment in the airways and an activation of the immune system that may contribute to the frequently recurrence of the respiratory disease. Infections of the URTI are the most common cause of viral morbidity in children. They represent the most frequent managed problem in general pediatric practice (1) and are responsible for more than one third of school absences (2). Many different immunologic problems can concur to the development of respiratory infections (3). Disorders of the aspecific humoral and the specific cellular defense are the principal cause of inflammation in the upper respiratory diseases (4). The recruitment and activation of inflammatory cells at the site of infection involve the expression of leukocyte and vascular adhesion molecules and the generation of pro-inflammatory cytokines, which contribute to the injury of lung epithelial and endothelial barriers (5). An important role in the early transient adhesion phases of leukocytes is mediated by the selectin family, which includes three distinct carbohydrate receptors expressed by either endothelial cells (E-selectin), leukocytes (L-selectin), or platelets and endothelial cells (P-selectin) (6). ICAM-1 and VCAM-1 are membrane glycoproteins, belonging to the immunoglobulin superfamily; ICAM-1 are widely expressed on respiratory epithelial cells, monocytes, macrophages, dendritic cells, and, together with VCAM-1, on vascular endothelial cells (7,8). These adhesion molecules, after a proteolytic cleavage, are found as so...

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“…Increased IL-10 production from monocytes was predictive of a recurrence of wheezing in children from the Netherlands [17]. Children from Rotterdam who developed wheezing in the first year of life had an increased IL-10/IL-12 ratio [28]. Finally, pro-inflammatory cytokines were observed in bronchoalveolar lavage fluid from infants in Finland with frequent wheeze [29].…”

Section: Discussionmentioning

confidence: 99%

Inflammatory markers predict episodes of wheezing during the first year of life in Bangladesh

Burgess

Jennie

et al. 2016

Respiratory Medicine

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Background Environmental factors that influence wheezing in early childhood in the developing world are not well understood and may be useful in predicting respiratory outcomes. Therefore, our objective was to determine the factors that can predict wheezing. Methods Children from Dhaka, Bangladesh were recruited at birth and episodes of wheezing were measured alongside nutritional, immunological and socioeconomic factors over a one-year period. Poisson Regression with variable selection was utilized to determine what factors were associated with wheezing. Results Elevated serum IL-10 (rate ratio (RR) = 1.51, 95% confidence interval (CI): 1.22–1.87), IL-1β (RR=1.55, 95% CI: 1.26–1.93) C-reactive protein (CRP) (RR=1.41, 95% CI: 1.03–1.93) in early life, and male gender (RR =1.52, 95% CI: 1.27–1.82) predicted increased wheezing episodes. Conversely, increased fecal alpha-1-antitrypsin (RR= 0.87, 95% CI: 0.76–1.00) and family income (RR=0.98, 95% CI: 0.97–0.99) were associated with a decreased number of episodes of wheezing. Conclusions Systemic inflammation early in life, poverty, and male sex placed infants at risk of more episodes of wheezing during their first year of life. These results support the hypothesis that there is a link between inflammation in infancy and the development of respiratory illness later in life and provide specific biomarkers that can predict wheezing in a low-income country.

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Increased serum IL‐10/IL‐12 ratio in wheezing infants

Cited by 13 publications

References 38 publications

Bronchoalveolar Lavage MMP-9 and TIMP-1 in Preschool Wheezers and Their Relationship to Persistent Wheeze

Bronchoalveolar Lavage MMP-9 and TIMP-1 in Preschool Wheezers and Their Relationship to Persistent Wheeze

Soluble Adhesion Molecules and Cytokines in Children Affected by Recurrent Infections of the Upper Respiratory Tract

Inflammatory markers predict episodes of wheezing during the first year of life in Bangladesh

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