Combination of minocycline and ciprofloxacin enhances the inhibitory effect of tumor necrosis factor-alpha production in lipopolysaccharide-stimulated THP-1 monocytic cells.

BACKGROUND

Tetracyclines, such as minocycline (MINO), are widely used in the treatment of infectious diseases. Japanese spotted fever (JSF) is usually treated with MINO. When MINO alone is ineffective in treating severe cases of JSF with complications, patients can be successfully treated with tetracycline combined with a quinolone such as ciprofloxacin (CPFX). However, the mechanisms underlying the efficacy of combination therapies remain unclear. We focused on cytokine suppression caused by antimicrobial agents.

METHODS

THP-1 cells (2 × 105/mL) were stimulated with 0.1 µg/mL lipopolysaccharide (LPS) and various concentrations of CPFX, MINO, or CPFX+MINO. TNF-α levels in the supernatant were measured using enzyme-linked immunosorbent assay (ELISA) after 4 h of stimulation.

RESULTS

MINO or CPFX alone significantly inhibited TNF-α and chemokine production, and their combination exerted an even greater inhibitory effect than either drug alone.

CONCLUSIONS

Combination therapy with MINO and CPFX enhanced the inhibitory effects on inflammatory cytokine and chemokine production in vitro. This combination therapy is expected to provide both antimicrobial and anti-inflammatory effects. Enhanced cytokine modulation by antibiotics may be a key mechanism in the treatment of severe infectious diseases such as JSF.