title: Suppressive efficacy of roxithromycin against human peripheral-blood mononuclear cells stimulated with hemolytic streptococci superantigen.
abstract: Bacterial colonization might influence the clinical response of psoriasis patients to the therapeutic efficacy of immunosuppressive drugs. Macroride antibiotics are used for the treatment of psoriasis patients; however, few studies have investigated the immunoregulatory efficacy of macrorides in bacterial superantigen-stimulated immune cells. The suppressive efficacy of roxithromycin was evaluated in vitro against the concanavalin A- or streptococcal pyrogenic enterotoxin A-induced proliferation of peripheral-blood mononuclear cells in 22 healthy subjects. The concentrations of ten cytokines in a peripheral-blood mononuclear cell-culture medium were measured using beads-array procedures. The cellular c-jun N-terminal kinase (JNK) activities were measured using cell-based ELISA procedures. Roxithromycin inhibited the proliferation of both concanavalin A- and superantigen-stimulated peripheral-blood mononuclear cells dose-dependently with significant effects at 50 microM (P<0.001). Furthermore, the suppressive efficacy of betamethasone butyrate propionate against the superantigen-stimulated peripheral-blood mononuclear cells were significantly promoted in combination with 5-25 microM roxithromycin (P<0.05). The concentrations of interleukin-2, -4, -5, -10 and -12p70 in the supernatant of the superantigen-stimulated peripheral-blood mononuclear cells cultured for 24 h and the concentrations for interleukin-1beta and -12p70 in the supernatant cultured for 72 h, respectively, decreased significantly in the presence of 50 microM roxithromycin (P<0.05). The stimulation of peripheral-blood mononuclear cells with the superantigen increased cellular JNK activity was significantly attenuated this increased activity by 50 microM roxithromycin (P<0.01). These results suggest that roxithromycin, either itself or in combination with glucocorticoid, is effective for the treatment of psoriasis patients with hemolytic streptococci infection, via the suppression of helper T lymphocytes by inhibiting the cellular JNK activity.
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Horinouchi, Tokyo, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Kamogawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kagami
authors.forename: Masaki
authors.initials: M
authors.lastname: Maeda
authors.forename: Kae
authors.initials: K
authors.lastname: Arai
authors.forename: Yukari
authors.initials: Y
authors.lastname: Okubo
authors.forename: Ryoji
authors.initials: R
authors.lastname: Tsuboi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000942:Antigens, Bacterial / Q000276:immunology* / Q000633:toxicity; D001623:Betamethasone / Q000031:analogs & derivatives / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D003208:Concanavalin A / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004338:Drug Combinations; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D053878:Hemolytic Agents / Q000633:toxicity*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D015575:Roxithromycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D016207:Cytokines; D004338:Drug Combinations; D053878:Hemolytic Agents; C117321:streptococcal superantigen SSA; D003208:Concanavalin A; D015575:Roxithromycin; D001623:Betamethasone; D048031:JNK Mitogen-Activated Protein Kinases