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

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 μM (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 μM 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-1β and -12p70 in the supernatant cultured for 72 h, respectively, decreased significantly in the presence of 50 μM 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 μM 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.