EFFECTS OF A NEW TOPIC AMIKACIN FORMULATION ON CHEMOTAXIS AND RELEASEOF PROFIBROTIC FACTORS BY HUMAN MONOCYTES

Aminoglycosides, widely used because of their large-spectrum antibioti c effects, should not interfere with the healing process of an ulcer o r an infected wound. We evaluated the effects of amikacin or the excip ients present in the topic formulation BG 90, powder 2.5% (Boniscontro e Gazzone S.r.l., Rome, Italy), on human monocyte chemotaxis and the release of profibrotic factors by resting or lipopolysaccharide (LPS)- activated monocytes. The chemotactic response of monocytes to zymosan- activated serum is not modified in vitro by pre-incubation of the cell s with amikacin (2 and 10 mu g/ml/10(6) cells) or excipients. Unstimul ated monocytes did not secrete appreciable amounts of cytokines. Vice versa, amikacin-stimulated cells released platelet-derived growth fact or AB (PDGF-AB) (about 340 pg/ml), transforming growth factor (TGF)-be ta 1 (about 10 pg/ml), and tumour necrosis factor (TNF)-alpha (over 1, 100 pg/ml); among excipients, ZnO and vitamin E induced PDGF-AB releas e (about 320 and, respectively, 200 pg/ml), while stimulation of monoc yte monolayers by the other excipients did not lead to appreciable cyt okine release. As expected, LPS-activated human monocytes produced PDG F-AB, TGF-beta 1, and TNF-alpha. When monocytes were co-stimulated wit h LPS and amikacin, the PDGFAB and TGF-beta 1 values almost overlapped with those from the stimulation of cells with LPS alone, while TNF-al pha production was slowly reduced. The results show a stimulating effe ct of aminoglycoside on the production of profibrotic factors and, the refore, on the healing process of wounds in addition to a modulating e ffect on the production of pro-inflammatory cytokines like TNF-alpha. Moreover, ZnO and tocopherol (free-radical scavengers), used as excipi ents in the topic formulation, induce the release of growth factors wi th profibrotic activity (PDGF-AB). Further research is warranted to ex plore the effects of this formulation in vivo, verifying whether the a ssociation of the antibiotic with scavengers has a double advantage in topical amikacin: on the one hand, it could limit the damage from fre e radicals, and on the other it could favour tissue healing.