Am. J. Respir. Cell Mol. Biol., Volume 20, Number 5, May, 1999 1007-1012

Anti-Inflammatory Actions of Interleukin-13
Suppression of Tumor Necrosis Factor- and Antigen-Induced Leukocyte Accumulation in the Guinea Pig Lung

Malcolm L. Watson, Anna-Marie White, Emma M. Campbell, Anthony W. Smith, Jasim Uddin, Teizo Yoshimura, and John Westwick

Department of Pharmacy and Pharmacology, University of Bath; Leukocyte Biology, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom; and Laboratory of Immunopathology, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland

The Th₂ cytokine interleukin (IL)-13 is believed to play an important role in the development of allergy, although it has also been ascribed anti-inflammatory roles in several experimental models. In this study, we have examined the effects of human recombinant IL-13 on eosinophilic lung inflammation in the guinea pig. IL-13 (1 to 100 ng, given by intratracheal instillation) did not elicit airway eosinophil recruitment. A pronounced accumulation of eosinophils, as well as monocyte/macrophages, was elicited by intratracheal instillation of guinea pig tumor necrosis factor alpha (gpTNF-). Intratracheal administration of IL-13 (1 to 100 ng) given immediately prior to exposure to gpTNF- resulted in a dose-related suppression of eosinophil and monocyte/macrophage accumulation in the airways, as assessed by bronchoalveolar lavage (BAL) and eosinophil peroxidase activity in whole-lung homogenates. IL-13 treatment also reduced BAL fluid (BALF) leukocyte accumulation induced by subsequent aerosol antigen challenge of sensitized guinea pigs. Antigen challenge also resulted in elevated levels of immunoreactive eotaxin and eosinophil-stimulating activity in BALF, although only the latter was reduced significantly by IL-13 instillation prior to challenge. In contrast to the suppressive effects of IL-13, instillation of human recombinant IL-4 (100 ng) alone elicited an increase in BALF monocyte/macrophage numbers, and IL-4 was unable to inhibit gpTNF--induced leukocyte accumulation. Hence, IL-13 (but not human IL-4) exhibits an anti-inflammatory action in the airways of gpTNF-- or antigen-challenged guinea pigs, by mechanisms that may involve the decreased generation of eosinophil-stimulating activity in the airways.

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