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      Interleukin-4 and 13 concentrations in infants at risk to develop Bronchopulmonary Dysplasia

      research-article
      1 , , 2 , 1
      BMC Pediatrics
      BioMed Central

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          Abstract

          Background

          An exaggerated inflammatory response occurs in the first few days of life in infants who subsequently develop bronchopulmonary dysplasia (BPD). The increase of inflammatory cytokines in many disease processes is generally balanced by a rise in anti-inflammatory cytokines. Interleukin-4 (IL-4) and interleukin-13 (IL-13) have been shown to inhibit production of several inflammatory cytokines important in the development of BPD.

          Methods

          We sought to determine if a correlation exists between the presence or absence of IL-4 and IL-13 in tracheal aspirates (TA) during the first 3 weeks of life and the development of BPD in premature infants. Serial TAs were prospectively obtained from 36 very low birth weight infants and IL-4 and IL-13 concentrations were determined by ELISA.

          Results

          Infants who developed BPD (n = 19) were less mature (25.3 ± 0.02 wks vs. 27.8 ± 0.05 wks; p < 0.001), and had lower birth weights (739 ± 27 g vs.1052 ± 41 g; p < 0.001). IL-4 and IL-13 were detectable in only 27 of 132 and 9 of 132 samples assayed respectively. Furthermore, the levels detected for IL-4 and IL-13 were very low and did not correlate with the development of BPD.

          Conclusions

          TA concentrations of IL-4 and IL-13 do not increase significantly during acute lung injury in premature infants.

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          Most cited references35

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          Interleukin-13: central mediator of allergic asthma.

          The worldwide incidence, morbidity, and mortality of allergic asthma are increasing. The pathophysiological features of allergic asthma are thought to result from the aberrant expansion of CD4(+) T cells producing the type 2 cytokines interleukin-4 (IL-4) and IL-5, although a necessary role for these cytokines in allergic asthma has not been demonstrable. The type 2 cytokine IL-13, which shares a receptor component and signaling pathways with IL-4, was found to be necessary and sufficient for the expression of allergic asthma. IL-13 induces the pathophysiological features of asthma in a manner that is independent of immunoglobulin E and eosinophils. Thus, IL-13 is critical to allergen-induced asthma but operates through mechanisms other than those that are classically implicated in allergic responses.
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            Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period.

            The follow-up records of 605 infants with birth weights of less than 1,500 g, with data available for 2 years after birth, were examined for evidence of abnormal pulmonary signs or symptoms. A total of 119 infants were identified and the neonatal oxygen requirements of these infants were compared with those of 486 infants who had normal pulmonary function. A requirement for oxygen at 28 days of life had a positive predictive value for abnormal pulmonary findings at the time of follow-up of only 38%, whereas 31% of those with normal pulmonary findings at the time of follow-up were still receiving oxygen at this age. The need for oxygen at 28 days was a good predictor of abnormal findings in infants of greater than or equal to 30 weeks' gestational age at birth but became increasingly less useful as gestational age decreased. It was found that, irrespective of gestational age at birth, the requirement for additional oxygen at 36 weeks' corrected postnatal gestational age was a better predictor of abnormal outcome, increasing the positive predictive value to 63%. The prediction of a normal outcome remained 90% for infants not receiving oxygen at this corrected gestational age.
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              Production of interleukin 13 by alveolar macrophages from normal and fibrotic lung.

              Human interleukin 13 (IL-13) is a cytokine that has a profound effect on primary immune cells by inducing immunoglobulin production, proliferation of B cells, and the differentiation of cells of the monocytic lineage. IL-13 can inhibit the production of inflammatory cytokines by both macrophages and monocytes. Previously, IL-13 expression has been reported only in cells of the T-cell lineage and the mast cell line HMC-1. We now report the presence of IL-13 mRNA and protein in human alveolar macrophages (AMs) analyzed by the reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunoabsorbent assay (ELISA), respectively, and IL-13 protein in bronchoalveolar lavage fluid (BALF) of subjects with pulmonary fibrosis. We have investigated 13 patients from 49 to 75 yr of age with forms of pulmonary fibrosis, and eight healthy volunteers from 24 to 61 yr of age. Their AMs were obtained by bronchoalveolar lavage (BAL) and purified by adherence. The proportion of BAL purified AMs expressing IL-13 mRNA was increased in those subjects with fibrotic lung disease, in comparison with those from control subjects (11 of 13 versus 2 of 8, P < 0.01). IL-13 protein was detectable in the BALF of 8 of 13 patients with pulmonary fibrosis, but in none of the control subjects. AMs of four subjects with systemic sclerosis were cultured and IL-13 protein was increased in the culture supernatants when compared to the control subjects, although this did not reach significance. These findings show that IL-13 mRNA is not only a product of T cells, but is also expressed in both normal AMs and those from subjects with pulmonary fibrosis, and that at least some of the IL-13 mRNA is translated into protein and secreted in subjects with pulmonary fibrosis. We hypothesize that IL-13 may be expressed by normal human AMs as part of the homeostatic control process but its production may be increased in the presence of inflammatory lung disease.
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                Author and article information

                Journal
                BMC Pediatr
                BMC Pediatrics
                BioMed Central (London )
                1471-2431
                2003
                18 August 2003
                : 3
                : 8
                Affiliations
                [1 ]Department of Pediatrics Louisiana State University Health Sciences Center 1501 Kings Highway Shreveport, Louisiana 71130-3932, USA
                [2 ]Louisiana State University Health Sciences Center 1501 Kings Highway, Shreveport, Louisiana 71130-3932, USA
                Article
                1471-2431-3-8
                10.1186/1471-2431-3-8
                194674
                12925236
                5a804900-329f-462f-b16d-feae9966ee72
                Copyright © 2003 Baier et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
                History
                : 28 March 2003
                : 18 August 2003
                Categories
                Research Article

                Pediatrics
                Pediatrics

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