title: Involvement of interleukin-18 (IL-18) in mixed lymphocyte reactions (MLR).
abstract: The in vitro mixed lymphocyte reaction (MLR) is a useful model to study alloresponsiveness to histocompatibility antigens. Secretion of different cytokine proteins in the supernatant of allo-MLR cultures has been reported in a few studies. We studied the levels of the cytokines interferon gamma (IFN-gamma) and interleukin-6 (IL-6), IL-10, IL-12, and IL-18 in the supernatant in allo-MLR by ELISA assay. Supernatant levels of IFN-y, IL-6, IL-10, and IL-18 were detected at 12 h after MLR and markedly increased thereafter. In contrast, secretion of IL-12 was detected after 48-72 h. These results suggested that IFN-gamma production depended on IL-18 in the early phase of MLR and depended on both IL-18 and IL-12 in the late phase. An antibody (Ab) neutralizing test was also performed. The levels of IFN-gamma were significantly downregulated after the addition of anti-IL-18 Ab, anti-IL-12 Ab, or anti-IFN-y Ab, and the levels of IL-12 were significantly downregulated after the addition of anti-IL-12 Ab and anti-IL-18 Ab. Treatment with these Ab did not suppress IL-6 production at all. The two-way MLR showed the same tendency as the one-way MLR. These results suggest the importance of IL-18 and IL-12 in allogeneic cell interactions and also suggest the usefullness of these Ab as regulators of alloresponsiveness.
authors.affiliation: First Department of Surgery, Okayama University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kohka
authors.forename: H
authors.initials: H
authors.lastname: Iwagaki
authors.forename: T
authors.initials: T
authors.lastname: Yoshino
authors.forename: K
authors.initials: K
authors.lastname: Kobashi
authors.forename: N
authors.initials: N
authors.lastname: Urushihara
authors.forename: T
authors.initials: T
authors.lastname: Yagi
authors.forename: T
authors.initials: T
authors.lastname: Tanimoto
authors.forename: M
authors.initials: M
authors.lastname: Kurimoto
authors.forename: T
authors.initials: T
authors.lastname: Akagi
authors.forename: N
authors.initials: N
authors.lastname: Tanaka
mesh_terms: D003470:Culture Media; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed
chemical_list: D003470:Culture Media; D020382:Interleukin-18; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma