The effect of ‘allergenic’ and ‘nonallergenic’ antibiotics on dog keratinocyte viability in vitro

Abstract

It appears that the effect of drugs on the in vitro viability of dog keratinocytes is not a good predictor of the 'allergenic' potential of an antibiotic. Further work is required to investigate other drug-induced 'danger' signals in dog keratinocytes exposed to 'allergenic' antibiotics in vitro.

Canine progenitor epidermal keratinocytes express various inflammatory markers, including interleukin‐8 and CD40, which are affected by certain antibiotics

“…The effect of enrofloxacin might have been even more important than observed, because at this concentration it kills almost 30% of CPEKs. 22 A prior study showed mRNA and protein levels of IL-8 to be increased in human monocyte-derived dendritic cells exposed to penicillins or sulfamethoxazole for 48 h. 72 Together with our data, this evidence suggests that it would be interesting to evaluate the effect of antibiotics on the expression of IL-8 in primary keratinocytes (especially in vivo). Interestingly, b-lactam and sulfonamide antibiotics are known to be associated commonly with hypersensitivity reactions in both humans and dogs, and these most commonly target the skin.…”

“…In an effort to mimic the in vivo situation, concentrations of antibiotics tested were selected based on previously published pharmacokinetic studies and in vitro toxicity investigations. 22 Specifically, our marker changes occurred repeatedly with enrofloxacin 500 lmol/L. Other studies have found cytotoxic effects in primary and immortalized cells with similar high concentrations of enrofloxacin.…”

“…Specifically, our marker changes occurred repeatedly with enrofloxacin 500 μmol/L. Other studies have found cytotoxic effects in primary and immortalized cells with similar high concentrations of enrofloxacin . Importantly, it is not uncommon for toxicologists to need to use higher doses in vitro to obtain an effect that would be seen at lower concentrations in vivo , especially when using immortalized cells .…”

“…[20][21][22] These concentrations were selected based on the expected plasma concentrations in vivo. 22 Certain experiments tested the highest concentration at 2, 4, 8 and 24 h.…”

“…In studies on canine cells, including keratinocytes, fluoroquinolone antibiotics have been found to decrease cell viability. [20][21][22] In addition, human keratinocytes have been shown to release reactive oxygen species and inflammatory cytokines in the presence of sulfonamide antibiotics. 23,24 To the best of our knowledge, the effects of antibiotics, or drugs in general, on inflammatory markers expressed by canine keratinocytes has yet to be investigated.…”