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.

No abstract

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.

No abstract

Roxithromycin (RXM), a new macrolide antibiotic, has a 14-member macrocycline ring structure which is similar to that of erythromycin. We investigated the effects of RXM on the proliferation of peripheral blood mononuclear cells (PBMCs) and the production of interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha) by PBMCs stimulated with lipopolysaccharide (LPS). At concentrations greater than 25.0 micrograms/ml, RXM suppressed the proliferation of PBMCs stimulated with phytohemagglutinin, probably due to cytotoxicity. When the PBMCs were incubated with RXM for 7 d, the number of adherent cells (monocyte/macrophages) increased. Incubation with RXM at a concentration of 25.0 micrograms/ml induced the greatest increase (p < 0.05). IL-1 beta and TNF-alpha were present 3 h after LPS-stimulation, and IL-1 beta production reached a peak at 12 h and TNF-alpha production at between 6 and 12 h, and then their production declined. RXM (25 micrograms/ml) suppressed the production of IL-1 beta and TNF-alpha slightly during the entire course of the incubation. This suppression was dose-dependent. Anti-human granulocyte-macrophage colony-stimulating factor and anti-human macrophage colony stimulating factor antibodies had no effect on the RXM-induced proliferation of adherent cells. Suppression of the production of IL-1 beta and TNF-alpha by RXM suggested that this drug might have anti-inflammatory and immunosuppressive effects.