Interleukin-4 increases the permeability of human endothelial cells in culture.
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.
Immunobiology and Infectious Diseases & Microbiology Units, Institute of Child Health, London, UK.
K
K
Kotowicz
R E
RE
Callard
N J
NJ
Klein
M G
MG
Jacobs
D002199:Capillary Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D012709:Serum Albumin / Q000378:metabolism
D012709:Serum Albumin; D015847:Interleukin-4