Broad-spectrum sunscreens prevent the secretion of proinflammatory cytokines in human keratinocytes exposed to ultraviolet A and phototoxic lomefloxacin

Abstract

The combination of phototoxic drugs and ultraviolet (UV) radiation can trigger the release of proinflammatory cytokines. The present study measured the ability of sunscreens to prevent cytokine secretion in human keratinocytes following cotreatment of these cells with a known photoreactive drug and UVA. Keratinocytes were treated for 1 h with increasing concentrations of lomefloxacin (LOM) or norfloxacin (NOR), exposed to 15 J/cm2 UVA, and incubated for 24 h. NOR, owing to the absence of a fluorine atom in position 8, was non-phototoxic and used as a negative control. Cell viability and the release of 3 cytokines were assessed, namely interleukin-1alpha (IL-1alpha), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha). The measurement of these cytokines may be a useful tool for detecting photoreactive compounds. To measure their ability to prevent cytokine secretion, various sunscreens were inserted between the UVA source and the cells. Treatment with NOR, NOR plus UVA, or LOM had no effect on the cells. LOM plus UVA, however, had an effect on cell viability and on cytokine secretion. IL-1alpha levels increased with LOM concentration. The release of TNF-alpha and IL-6 followed the same pattern at lower concentrations of LOM but peaked at 15 micromol/L and decreased at higher concentrations. Sunscreens protected the cells from the effects of LOM plus UVA, as cell viability and levels of cytokines remained the same as in the control cells. In conclusion, the application of broad-spectrum sunscreen by individuals exposed to UVA radiation may prevent phototoxic reactions initiated by drugs such as LOM.

Identification of Genes Responsive to Solar Simulated UV Radiation in Human Monocyte-Derived Dendritic Cells

“…Solar-simulated radiation of DCs increased the expression of several inflammatory cytokines. Keratinocytes, in addition to DCs, are known to produce and secrete a large number of proinflammatory soluble factors, such as IL-1, IL-5, IL-8, TNF-alpha and prostaglandin E2, thus participating in the onset of inflammation and the induction of chemotaxis to the skin [29], [30]. Accordingly, genes such as IL-1A and IL-B were up-regulated in keratinocytes, whereas mRNA expression of these cytokines was undetectable in melanocytes under our experimental conditions.…”

Photosensitization Reactions of Fluoroquinolones and Their Biological Consequences

“…This model (diameter = 8 mm) consists of normal human‐derived keratinocytes, multiple viable cell layers, functional stratum corneum. Other in vitro tests confirmed LOM photocytotoxicity, as measured by cell viability and cytokines release (90). CIP photocytotoxicity was confirmed by a panel of tests including NR and MTT (3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assays (84).…”