title: Anti-inflammatory actions of interleukin-13: suppression of tumor necrosis factor-alpha and antigen-induced leukocyte accumulation in the guinea pig lung.
abstract: 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-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 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-alpha-induced leukocyte accumulation. Hence, IL-13 (but not human IL-4) exhibits an anti-inflammatory action in the airways of gpTNF-alpha- or antigen-challenged guinea pigs, by mechanisms that may involve the decreased generation of eosinophil-stimulating activity in the airways.
authors.affiliation: 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. m.l.watson@bath.ac.uk
authors.forename: M L
authors.initials: ML
authors.lastname: Watson
authors.forename: A M
authors.initials: AM
authors.lastname: White
authors.forename: E M
authors.initials: EM
authors.lastname: Campbell
authors.forename: A W
authors.initials: AW
authors.lastname: Smith
authors.forename: J
authors.initials: J
authors.lastname: Uddin
authors.forename: T
authors.initials: T
authors.lastname: Yoshimura
authors.forename: J
authors.initials: J
authors.lastname: Westwick
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D000941:Antigens / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002449:Cell Aggregation; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000166:cytology* / Q000201:enzymology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology* / Q000627:therapeutic use; D008168:Lung / Q000201:enzymology / Q000473:pathology*; D008297:Male; D010544:Peroxidases / Q000378:metabolism; D011014:Pneumonia / Q000628:therapy; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000941:Antigens; D018793:Interleukin-13; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D047209:Eosinophil Peroxidase; D010544:Peroxidases