The effects of β-adrenoceptor agonists (β-agonists) on the production of tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1β) and interleukin-8 (IL-8) by lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs) were investigated. The β-agonists, procaterol, clenbuterol, fenoterol and terbutaline, inhibited TNF-α and IL-1β production in a concentration-dependent manner, whereas they had no effect on IL-8 production. TNF-α production was inhibited more potently than IL-1β. Dibutyryl cyclic AMP (dbcAMP) also inhibited the production of TNF-α and IL-1β, but not IL-8. TNF-α production was almost completely inhibited by dbcAMP, whereas IL-1β production appeared to be partially refractory even at the highest concentration examined. Both procaterol and the-ophylline elevated cAMP levels in LPS-stimulated PBMCs, but the effect of procaterol was limited. The inhibition of TNF-α and IL-1β production by procaterol was additively potentiated with theophylline. dl-Propranolol, a β-adrenoceptor antagonist, abrogated the inhibition of TNF-α and IL-1β production by procaterol. These results indicate that β-agonists inhibit the production of proinflammatory cytokines, such as TNF-α and IL-1β, by elevating intracellular cAMP levels. These properties of β-agonists might be beneficial in the treatment of allergic inflammation.

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Levofloxacin (LVFX), the bacteriologically active isomer of ofloxacin, is a fluorinated quinolone. LVFX suppressed the proliferative activity of peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin (PHA). LVFX increased interleukin-2 (IL-2) production by PBMC stimulated with PHA in a dose-dependent manner, with more than 10 μg/ml of LVFX causing a significant increase. The granulocyte-macrophage colony-stimulating factor and soluble IL-2 receptor production by PHA-stimulated PBMC was suppressed at high concentrations of LVFX. Interleukin-1β production by lipopolysaccharide-stimulated PBMC was suppressed in a concentration-dependent manner by LVFX, and tumor necrosis factor-α production was suppressed at only the highest concentration. In contrast, interleukin-8 production was little affected by LVFX. These results show that LVFX has an immunomodulatory action on cytokines production by PBMC independent of its antimicrobial activity.

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