Am. J. Respir. Cell Mol. Biol., Volume 20, Number 3, March, 1999 474-480

Synergistic Effects of Interleukin-4 or Interleukin-13 and Tumor Necrosis Factor- on Eosinophil Activation In Vitro

Werner Luttmann, Timm Matthiesen, Heinrich Matthys, and Johann Christian Virchow Jr.

Department of Pneumology, Medical University Clinics, Freiburg, Germany

Increased concentrations of tumor necrosis factor- (TNF-), interleukin (IL)-4, and IL-13 have been measured in bronchoalveolar lavage fluid (BALF) of patients with asthma following allergen provocation. In addition, these cytokines have also been reported to activate eosinophils in vitro. Although cytokine interactions have been postulated in the activation of eosinophils, the combined effects of cytokines on eosinophil activation remain poorly understood. Because activation of eosinophils has been regarded as a crucial event in the pathogenesis of asthmatic inflammation, we tested the hypothesis that IL-4 and IL-13 could enhance the effects of TNF- on eosinophil activation. For this purpose, eosinophils from normal donors were purified and cultured in the presence of IL-4 or IL-13 and TNF-. Eosinophil survival and surface expression of CD69 were assessed by flow cytometry. There was a concentration- and time-dependent upregulation in CD69 expression as well as eosinophil survival when eosinophils were incubated with IL-13, IL-4, or TNF-. However, eosinophil viability and CD69 expression increased synergistically when eosinophils were incubated with IL-13 or IL-4 in the presence of TNF-. This synergistic effect of IL-4 and IL-13 on CD69 expression was not limited to TNF- but was also observed with IL-5. Our study provides evidence that IL-4 can activate eosinophils in a similar fashion as does IL-13. Furthermore, this study shows that the addition of IL-4 or IL-13 to TNF- or IL-5 has synergistic effects on eosinophil activation, suggesting that the combined effects of different cytokines present in BALF following allergen provocation can enhance eosinophil activation in vitro.

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