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Inhibition of in vitro immunoglobulin production by IL-12 in murine chronic graft-vs.-host disease: synergism with IL-18.

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Lauwerys, Bernard [UCL] Renauld, Jean-Christophe [UCL] Houssiau, Frédéric [UCL]

We investigated the effects of IL-12 on immunoglobulin (Ig) production in vitro in murine chronic graft-vs. -host disease (cGVHD), a lupus-like model of overt B cell activation induced by allogeneic stimulation. Addition of IL-12 to cGVHD splenocytes strongly inhibited total Ig (Igkappa), IgM and IgG1 production. Although IL-12 down-regulated IL-4, IL-5, IL-9 and IL-10 production, its inhibitory activity on Ig production could not be ascribed to down-regulation of these cytokines, as addition of saturating doses of IL-4, IL-5 and/or IL-9 did not reverse the inhibitory activity of IL-12. Interestingly, IL-12 was also found to suppress the stimulating effect of IL-4 and IL-5 on Ig synthesis by cGVHD splenocytes. Several lines of evidence indicated that the inhibitory activity exerted by IL-12 on Ig production was mediated by IFN-gamma. First, IFN-gamma was produced in large amounts upon IL-12 stimulation. Secondly, it displayed a potent inhibitory activity on Ig production. Thirdly, Ig production was also inhibited by IL-18, a recently cloned IFN-gamma-inducing cytokine. Finally, the inhibitory activity of IL-12 was blocked by anti-IFN-gamma monoclonal antibody. We also investigated whether IL-12 down-regulated Ig production by purified cGVHD B cells. We found that IL-12 had only a marginal inhibitory activity on highly purified B cell populations isolated from cGVHD splenocytes and stimulated with IL-4 and IL-5, and that IL-18 was inactive in this respect. However, when the two cytokines were combined, a striking synergy was unmasked not only for IgG1 inhibition but also for IFN-gamma production by these B cell populations. Taken together, our results demonstrate that IL-12 inhibits in vitro Ig production by activated splenocytes through IFN-gamma production and that it synergizes with IL-18 on activated B cells to inhibit Ig production, through up-regulation of IFN-gamma production by B cells.

Document type Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't
Access type Accès restreint
Publication date 1998
Journal information "European journal of immunology" - Vol. 28, no. 6, p. 2017-24 (1998)
Peer reviewed yes
issn 0014-2980
Publication status Publié
Affiliation UCL - MD/MINT - Département de médecine interne
MESH Subject Animals ; Antibody Formation ; B-Lymphocytes - drug effects - immunology ; Cells, Cultured ; Chronic Disease ; Cytokines - immunology - pharmacology ; Down-Regulation ; Graft vs Host Disease - immunology ; Interferon-gamma - immunology - pharmacology ; Interleukin-12 - immunology - pharmacology ; Interleukin-18 ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Spleen - cytology - metabolism ; Th2 Cells - immunology ; Up-Regulation
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Bibliographic reference Lauwerys, Bernard ; Renauld, Jean-Christophe ; Houssiau, Frédéric. Inhibition of in vitro immunoglobulin production by IL-12 in murine chronic graft-vs.-host disease: synergism with IL-18.. In: European journal of immunology, Vol. 28, no. 6, p. 2017-24 (1998)
Permanent URL http://hdl.handle.net/2078.1/27550