Stimulatory effects of dibutyryl cyclic adenosine monophosphate on cytokine production by keratinocytes and fibroblasts.

Abstract

Clinical studies have shown that ointment containing dibutyryl cyclic adenosine monophosphate (DBcAMP) promotes wound healing. We aimed to elucidate the mechanisms of the beneficial effect of DBcAMP in wound healing. An investigation was made of the effects of DBcAMP on in vitro cytokine release from cultured keratinocytes and fibroblasts derived from normal human skin. DBcAMP stimulated keratinocyte proliferation through increased interleukin (IL)-6 production by fibroblasts, and transiently enhanced production of transforming growth factor (TGF)-beta1 by fibroblasts at an early stage of incubation. DBcAMP also stimulated fibroblast proliferation, resulting in further increases in IL-6 and TGF-beta1. We conclude that this series of stimulative actions on cytokine secretion, together with the facilitation of cell proliferation, contribute to the effects of DBcAMP on the healing of skin ulcers.