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Impairment of Leukocyte Trafficking in a Murine Pleuritis Model by IL-4 and IL-10

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Abstract

We have characterized leukocyte migration to the pleural cavity in a methylated-BSA (mBSA)-induced model of murine delayed-type hypersensitivity and evaluated the ability of IL-4 and IL-10 to modulate this response. Neutrophils, macrophages, T cells, and dendritic cells migrated to the pleural cavity in a time-dependent fashion following direct intrapleural antigen challenge, with neutrophils comprising the majority of exudate leukocytes in the cavity within the first 24 h and the number of mononuclear cells increasing at later times. Real-time quantitative PCR analysis of infiltrating leukocytes revealed a marked elevation of steady-state mRNA levels of IL-1β and TNFα and the chemokines KC, MIP-2, CXCL9, CXCL10, CXCL11, CCL2, CCL3, and CCL4 at 6 h postchallenge, which diminished over time. In contrast, γIFN mRNA levels were maximal at 24 h and CCL5 expression was sustained throughout 72 h. ELISA analysis of pleural exudate fluid revealed significant elevations of KC and CCL2 protein levels at 6 h postantigen challenge and a peak increase in γIFN protein at 24 h, confirming our mRNA observations. Administration of recombinant murine IL-4 or IL-10 prior to challenge significantly blocked cell trafficking to the pleural cavity as well as peak levels of exudate γIFN, with IL-4 being more potent in impairing these responses. IL-4 administration also increased the proportion of naïve T cells in the pleural cavity, as judged by CD62L and CD45RB expression. These results indicate that this in vivo model demonstrates a pattern of events associated with Th1-mediated leukocyte trafficking and underscore the potential utility of this in vivo model for evaluating therapeutic inhibitors of leukocyte trafficking.

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Authors and Affiliations

  1. Department of Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey

    Jay S. Fine, Alberto Rojas-Triana, James V. Jackson, Laura W. Engstrom, Gregory S. Deno, Daniel J. Lundell & Loretta A. Bober

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  1. Jay S. Fine
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Correspondence to Jay S. Fine.

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Fine, J.S., Rojas-Triana, A., Jackson, J.V. et al. Impairment of Leukocyte Trafficking in a Murine Pleuritis Model by IL-4 and IL-10. Inflammation 27, 161–174 (2003). https://doi.org/10.1023/A:1025076111950

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