Anti-inflammatory and antiproliferating properties of allylamines

Terbinafme (TB, SF86-327), a synthetic allylamine, is a broad-spectrum, orally active antifungal. Cytospin data showed that TB-treated (10-50 ug/ml for 30 min at 37 °C) human polymorphonuclear leukocytes (PMNs) displayed nuclear rounding with loss of lobulations and a reduction in the cytoplasmic to nuclear ratio. Similar cytoplasmic to nuclear ratio reductions were also demonstrated in TB-treated peripheral blood lymphocytes (PBLs). TB-treated PMNs (at > 25 ng/ml) exhibited normal respiratory burst activity measured by Superoxide anion production and chemiluminescence (CL), but showed reduced chemotaxis (CT). TB significantly (p < 0.01-0.05) inhibited PMN and PBL adhesion to human microvascular endothelium (HMEC-1). The TB-treated leukocytes were stimulated by chemotactic factors or mitogens, and cell adhesion was measured by uptake of rose bengal stain using an ELISA reader. TB analogues (85-190 or naftifine) produced similar dose-dependent inhibitory effects on CT and cell adhesion to HMEC-1, the latter also inhibited CL. Cell cycle flow cytometric analysis showed doseand time-dependent alterations in Gl and/or G2+M phase(s) consistent with cell cycle and mitotic blockade in mitogen-activated PBLs and a promyelocytic cell line (HL60). Our data collectively demonstrates morphological and functional differences among allylaminetreated cells, which may explain many of the antiinflammatory and antiproliferation effects.