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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.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Kamogawa S,Kagami K,Maeda M,Arai K,Okubo Y,Tsuboi R,Hirano T

doi

10.1016/j.ejphar.2008.11.045

subject

Has Abstract

pub_date

2009-01-14 00:00:00

pages

439-47

issue

2-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(08)01200-4

journal_volume

602

pub_type

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Suppressive efficacy of roxithromycin against human peripheral-blood mononuclear cells stimulated with hemolytic streptococci superantigen.