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Interleukin-4 increases the permeability of human endothelial cells in culture

Authors


Dr Michael Jacobs, Centre for Hepatology, Royal Free & University College Medical School, Rowland Hill Street, London NW3 2PF, UK. E-mail: michael.jacobs@rfc.ucl.ac.uk

Summary

Background IL-4 plays a key role in the induction of allergic inflammation, but its role as an effector molecule is less well-established. Although some observations suggest that IL-4 may mediate increased vascular permeability, which is a characteristic feature of allergic inflammation, evidence for a direct effect on endothelial cell permeability is lacking.

Objective To determine the effect of human IL-4 on the albumin permeability of cultured human endothelial cells.

Methods Human umbilical vein endothelial cells were cultured on permeable membranes and the albumin permeability of endothelial monolayers was measured with and without exposure to recombinant human IL-4. Endothelial cells were exposed to various concentrations of IL-4 (0.001–100 U/mL), for various durations (6–24 h), either in the presence or absence of anti-IL-4 antibody. Recovery of endothelial barrier function following exposure to IL-4 was also examined.

Results IL-4 induced a dose-dependent, reversible increase in endothelial permeability to albumin. Low concentrations of IL-4 (1 U/mL) induced a significant increase in endothelial permeability (P=0.004). IL-4-mediated endothelial leak occurred rapidly, within 6 h of exposure.

Conclusions IL-4 has the capacity to induce vascular leak by a direct effect on cultured endothelial cells, suggesting a potential effector role for IL-4 in the pathogenesis of vascular leak in allergic diseases.

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