Effects of granulocyte-macrophage colony stimulating factor (GM-CSF) in vivo on cytokine production and proliferation by spleen cells

Authors

  • S. Khatami,

    1. California Institute for Medical Research,
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  • E. Brummer,

    1. California Institute for Medical Research,
    2. Division of Infectious Diseases, Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA, and
    3. Stanford, University School of Medicine, Stanford, CA, USA
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  • D. A. Stevens

    1. California Institute for Medical Research,
    2. Division of Infectious Diseases, Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA, and
    3. Stanford, University School of Medicine, Stanford, CA, USA
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Dr Elmer Brummer, Division of Infectious Diseases, Department of Medicine, Santa Clara Valley Medical Center, 751 South Bascom Ave., San Jose, CA 95128–2699, USA.  E-mail: e.brummer@juno.com

Abstract

GM-CSF is a potent stimulator of haematopoietic cells as well as some functions of granulocytes and macrophages. GM-CSF has many clinical uses; however, little is known about the effects of GM-CSF treatment in vivo on the responses of tissue lymphocytes in terms of secretion of Th-1 and Th-2 cytokines. We investigated this issue by measuring the responses of spleen cells from mice 24 h after treatment i.p. with saline or rmGM-CSF. GM-CSF at 16·7–50·0 µg/kg significantly increased (P < 0·01) spleen cellularity 2–2·5-fold and enhanced proliferative responses of non-stimulated (no mitogen) as well as concanavalin A (Con A)-stimulated spleen cells. Secretion of IFN-γ by Con A (2·5 µg/ml)-stimulated spleen cells was significantly (P < 0·01) increased from 1·8 µg/ml by control spleen cells to 5·2 μg/ml by GM-CSF spleen cells. IL-10 production was greater (0·25 μg/ml, P < 0·05) by Con A-stimulated spleen cells from GM-CSF-treated mice compared to control spleen cells (0·06 μg/ml). By contrast, there were no significant differences in IL-4 production by Con A-stimulated spleen cells from the different groups. These results show that GM-CSF treatment increases spleen cellularity and primes lymphocytes for enhanced responses. The enhanced production of Th-1 cytokines by primed lymphocytes may partially explain the beneficial role of in vivo administration of GM-CSF in several clinical situations.

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