Anti-inflammatory actions of interleukin-13 - Suppression of tumor necrosis factor-alpha and antigen-induced leukocyte accumulation in the guinea piglung

The Th-2 cytokine interleukin (IL)-13 is believed to play an important role in the development of allergy, although it has also been ascribed anti-inf lammatory roles in several experimental models. In this study, we have exam ined the effects of human recombinant IL-13 on eosinophilic lung inflammati on in the guinea pig. IL-13 (1 to 100 ng, given by intratracheal instillati on) did not elicit airway eosinophil recruitment. A pronounced accumulation of eosinophils, as well as monocyte/macrophages, was elicited by intratrac heal instillation of guinea pig tumor necrosis factor alpha (gpTNF-alpha). Intratracheal administration of IL-13 (1 to 100 ng) given immediately prior to exposure to gpTNF-alpha resulted in a dose-related suppression of eosin ophil and monocyte/macrophage accumulation in the airways, as assessed by b ronchoalveolar lavage (BAL) and eosinophil peroxidase activity in whole-lun g homogenates. IL-13 treatment also reduced BAL fluid (BALF) leukocyte accu mulation induced by subsequent aerosol antigen challenge of sensitized guin ea pigs. Antigen challenge also resulted in elevated levels of immunoreacti ve eotaxin and eosinophil-stimulating activity in BALF, although only the l atter was reduced significantly by IL-13 instillation prior to challenge. I n contrast to the suppressive effects of IL-13, instillation of human recom binant IL-4 (100 ng) alone elicited an increase in BALF monocyte/macrophage numbers, and IL-4 was unable to inhibit gpTNF-alpha-induced leukocyte accu mulation. Hence, IL-13 (but not human IL-4) exhibits an anti-inflammatory a ction in the airways of gpTNF-alpha- or antigen-challenged guinea pigs, by mechanisms that may involve the decreased generation of eosinophil-stimulat ing activity in the airways.