title: Comparative study of the effects of betamethasone butyrate propionate, vitamin D3 derivatives, and cyclosporine on human lymphocyte-proliferation stimulated with a hemolytic streptococci-derived superantigen.
abstract: Bacterial infection might influence the clinical response of patients with immunological disorders including psoriasis to the therapeutic efficacies of immunosuppressive drugs, but few studies have been carried out to investigate the implication of bacterial superantigens. We evaluated the suppressive efficacies of betamethasone butyrate propionate, vitamin D3 derivatives, and cyclosporine against concanavalin A- or superantigen-induced proliferation of peripheral-blood mononuclear cells obtained from 18 healthy subjects. In vitro drug concentrations giving 50% inhibition (IC50s) of peripheral-blood mononuclear cell-proliferation stimulated with concanavalin A or streptococcal pyrogenic enterotoxin A were estimated. Concentrations of tumor necrosis factor-alpha, interferon-gamma, interleukin-2, -4, -5, or -10, in a peripheral-blood mononuclear cell-culture medium were measured with beads-array procedures. The median (range) IC50 value for betamethasone butyrate propionate evaluated in the streptococcal pyrogenic enterotoxin A-stimulated peripheral-blood mononuclear cells was 291.6 (0.001-1171.5) ng/ml, which was significantly higher than the value 0.072 (0.01-222.5) ng/ml found in concanavalin A-stimulated peripheral-blood mononuclear cells (P=0.0245). However, the median (range) IC50 value for calcipotriol in the streptococcal pyrogenic enterotoxin A-stimulated peripheral-blood mononuclear cells was 0.3 (0.24-1357.4) ng/ml, which was significantly lower than the value 128.6 (0.1-776.9) ng/ml found in concanavalin A-stimulated peripheral-blood mononuclear cells (P=0.0323). The IC50 value for cyclosporine was not significantly different between the concanavalin A- and streptococcal pyrogenic enterotoxin A-stimulated PBMCs. Concentration for none of the cytokines was significantly different between concanavalin A- and streptococcal pyrogenic enterotoxin A-stimulated peripheral-blood mononuclear cell cultures. The effects of betamethasone butyrate propionate to suppress these cytokine productions were rather stronger than those of calcipotriol. Streptococcal pyrogenic enterotoxin A induced by hemolytic streptococci colonization is suggested to attenuate the therapeutic efficacy of betamethasone butyrate propionate. While the mechanistic background of calcipotriol to suppress streptococcal pyrogenic enterotoxin A-induced peripheral-blood mononuclear cell-proliferation remains to be elucidated, vitamin D3 derivatives appears to be effective in suppressing anomalistic immunity in patients having hemolytic streptococci colonization.
authors.affiliation: Department of Dermatology, Tokyo Medical University, Japan.
authors.forename: Kae
authors.initials: K
authors.lastname: Arai
authors.forename: Terumi
authors.initials: T
authors.lastname: Uchiyama
authors.forename: Yukari
authors.initials: Y
authors.lastname: Okubo
authors.forename: Ryoji
authors.initials: R
authors.lastname: Tsuboi
authors.forename: Kitaro
authors.initials: K
authors.lastname: Oka
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000328:Adult; D001623:Betamethasone / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D003208:Concanavalin A / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000378:metabolism; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D011565:Psoriasis / Q000188:drug therapy; D013291:Streptococcus / Q000276:immunology*; D018089:Superantigens / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004768:Enterotoxins; D007166:Immunosuppressive Agents; D007378:Interleukins; D008934:Mitogens; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D002762:Cholecalciferol; D007371:Interferon-gamma; D016572:Cyclosporine; D001623:Betamethasone