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Effect of interleukin 8 in meconium on in-vitro neutrophil chemotaxis
A J de Beaufort1, D M Pelikan, J G Elferink
1Neonatal Unit, Department of Paediatrics, Leiden University Medical Centre, The Netherlands. AdBeaufort@KINDJC.AZL.NL
Background:
Pneumonitis, characterised by large numbers of neutrophils in the lung, is an important feature of the meconium aspiration syndrome. The mechanism underlying the neutrophil influx is not known. We have investigated whether meconium has chemotactic activity and whether such activity is related to the presence of interleukin 8.
Methods:
The chemotactic activity of meconium on neutrophils from newborn infants was assessed in a Boyden-chamber assay. Interleukin 8 and formyl-methionyl-leucyl-phenylalanine (f-MLP) served as positive controls. Inhibition of chemotaxis was assessed with monoclonal antibody to interleukin 8. The interleukin-8 concentration was measured by ELISA.
Findings:
Sterile meconium suspension from seven unrelated newborn babies increased migration of neutrophils from neonates in comparison with random migration (79, 72, 70, 50, 58, 88 microm vs 46 microm; p<0.001). This effect was greatest at a meconium concentration of 5 g/L, although differences between samples from individual babies were observed. Interleukin 8 was present in all meconium suspensions (480-3980 ng/L). Anti-interleukin-8 inhibited neutrophil migration.
Interpretation:
Interleukin 8 is present in meconium and it induces chemotaxis of neutrophils in vitro. This mechanism may have a role in the pathogenesis of pneumonitis in meconium aspiration syndrome.
Insights
Meconium causes neutrophil migration in the lungs, a key factor in meconium aspiration syndrome pneumonitis. This is due to the presence of interleukin 8 in meconium, which attracts neutrophils.
Area of Science:
- Neonatal immunology
- Respiratory medicine
- Inflammatory processes
Background:
- Pneumonitis is a significant complication of meconium aspiration syndrome, characterized by neutrophil infiltration in the lungs.
- The precise mechanisms driving neutrophil influx in this condition remain unclear.
Purpose of the Study:
- To investigate the potential chemotactic activity of meconium on neutrophils.
- To determine if interleukin 8 is involved in meconium-induced neutrophil chemotaxis.
Main Methods:
- Assessed meconium's chemotactic effect on neonatal neutrophils using a Boyden-chamber assay.
- Measured interleukin 8 concentrations via ELISA and assessed chemotaxis inhibition using an anti-interleukin 8 antibody.
Main Results:
- Meconium suspensions significantly increased neutrophil migration compared to random movement (p<0.001).
- Interleukin 8 was detected in all meconium samples (480-3980 ng/L), and anti-interleukin 8 antibodies inhibited neutrophil migration.
Conclusions:
- Interleukin 8 is present in meconium and actively induces neutrophil chemotaxis in vitro.
- This interleukin 8-mediated neutrophil recruitment may play a role in the development of pneumonitis associated with meconium aspiration syndrome.