key: cord-322332-0pi3wcv5
authors: Conforti, Claudio; Giuffrida, Roberta; Zalaudek, Iris; Di Meo, Nicola
title: Doxycycline, a widely used antibiotic in dermatology with a possible anti‐inflammatory action against IL‐6 in COVID‐19 outbreak
date: 2020-05-15
journal: Dermatol Ther
DOI: 10.1111/dth.13437
sha: 
doc_id: 322332
cord_uid: 0pi3wcv5

nan

) is the protagonist of cytokines that are activated as a result of a dysregulated host immune response at alveolar level, which may contribute to the development of a pulmonary parenchymal inflammation with consequent lung interstitiopathy causing a reduction in respiratory function. 5 The efficacy and safety of a number of IL-6 receptor antibodies are currently under investigation, with no definitive results available at the moment.

An open-label nonrandomized clinical trial suggested that chloroquine and its less toxic metabolite, hydroxychloroquine, may be effective against COVID-19. 6 Gautret et al supported the synergistic effect of the combination of hydroxychloroquine (200 mg × 3/day for 10 days) and the macrolide antibiotic azithromycin (500 mg on the first day then 250 mg/day for 5 more days) that is known to have a broad spectrum of action against most causes of pneumonia, as well as a potential anti-inflammatory effect. 6 Since then, many authors described the abovementioned combination as therapeutic or prophylactic in the SARS-CoV-2 pandemic.

In view of this, doxycycline (a semisynthetic derivative of tetracycline) would seem to be a valid alternative to azithromycin. In fact, in addition to its well-defined antibiotic effects (bacteriostatic action by inhibition of bacterial protein synthesis), in vitro studies have shown doxycycline to exert anti-inflammatory effects at low (20-40 mg/day) and high (100 or 200 mg/day) doses with inhibitory action on metalloproteases and modulating effects of pro-inflammatory cytokines IL-6, IL-8, and tumor necrosis factor-alpha. 7 The anti-inflammatory properties of doxycycline and other components of tetracycline has been demonstrated for several inflammatory airway diseases, including, acute respiratory distress syndrome. 8 Thereby, low doxycycline doses have been shown to be more effective than high doses to prevent induction of pro-inflammatory cytokines (such as IL-6) in inflammatory diseases. 7 Doxycycline is rapidly and almost completely absorbed after oral administration. It is a safe and inexpensive drug with a minimal toxicity. 7 The most common side effects are gastrointestinal (stomach pain, nausea, vomiting, diarrhea, and gastritis) and dermatological (rash, sensitivity to the sun). 7 Doxycycline is contraindicated during pregnancy due to its potential adverse teratogenic effects and in children under 

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