Sulfur Mustard (HD) is a potent vesicating agent that leads to an increased production of IL-8 in HD-exposed human epidermal keratinocytes (HEK). The present study examined IL-8 production over a 24-h period in HEK cells exposed to HD (200 μM) and treated 1 h after exposure with either doxycycline or minocycline. To test the involvement of iron chelation in the anti-inflammatory action of tetracyclines, we treated thes HEK cells with a combination of either N,N’-bis(2-hydroxybenzyl)-ehtylenediamine-N,N’-diacetic acid (HBED) or 1,2-dimethyl-3-hydroxypyridin-4-one (L1) with 50 μM doxycycline. We found that either 100 μM doxycycline alone or 100 μM minocycline alone reduced IL-8 release to untreated control levels. In the presence of 50 μM doxycycline, the ED50 of the drug, we found that 10 μM HBED reduced IL-8 release to control levels, while equal 10 μM L1 treatment did not significantly affect IL-8 release. This result suggests that some part of the ability of doxycycline to inhibit IL-8 release is related to prevention of iron redox cycling and not simply to iron chelation.