Effects of a new topic amikacin formulation on chemotaxis and release of profibrotic factors by human monocytes.
Aminoglycosides, widely used because of their large-spectrum antibiotic effects, should not interfere with the healing process of an ulcer or an infected wound. We evaluated the effects of amikacin or the excipients 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 cells with amikacin (2 and 10 microg/ml/10(6) cells) or excipients. Unstimulated monocytes did not secrete appreciable amounts of cytokines. Vice versa, amikacin-stimulated cells released platelet-derived growth factor AB (PDGF-AB) (about 340 pg/ml), transforming growth factor (TGF)-beta1 (about 10 pg/ml), and tumour necrosis factor (TNF)-alpha (over 1,100 pg/ml); among excipients, ZnO and vitamin E induced PDGF-AB release (about 320 and, respectively, 200 pg/ml), while stimulation of monocyte monolayers by the other excipients did not lead to appreciable cytokine release. As expected, LPS-activated human monocytes produced PDGF-AB, TGF-beta1, and TNF-alpha. When monocytes were co-stimulated with LPS and amikacin, the PDGF-AB and TGF-beta1 values almost overlapped with those from the stimulation of cells with LPS alone, while TNF-alpha production was slowly reduced. The results show a stimulating effect of aminoglycoside on the production of profibrotic factors and, therefore, on the healing process of wounds in addition to a modulating effect on the production of pro-inflammatory cytokines like TNF-alpha. Moreover, ZnO and tocopherol (free-radical scavengers), used as excipients in the topic formulation, induce the release of growth factors with profibrotic activity (PDGF-AB). Further research is warranted to explore the effects of this formulation in vivo, verifying whether the association of the antibiotic with scavengers has a double advantage in topical amikacin: on the one hand, it could limit the damage from free radicals, and on the other it could favour tissue healing.
Istituto di Clinica Dermosifilopatica, Facoltà di Medicina e Chirurgia, Seconda Università degli Studi di Napoli, Italia.
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Baroni
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Tufano
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Bolognino
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Buttini
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Catalanotti
D000287:Administration, Topical; D000583:Amikacin / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C095477:platelet-derived growth factor AB; D000583:Amikacin