MONOCYTE PHOSPHODIESTERASE ABNORMALITIES AND DYSREGULATION OF LYMPHOCYTE FUNCTION IN ATOPIC-DERMATITIS

The immunologic aberrations associated with atopic dermatitis include the paradox of reduced cell-mediated immune responses in the setting o f increased cell-mediated immunity features that resemble allergic con tact dermatitis. In this review, we present evidence that abnormalitie s in monocytes and Langerhans cells alter the function of T-helper-cel l subpopulations to cause the immunologic defects associated with atop ic dermatitis, Increased monocyte prostaglandin E(2) production inhibi ts Th1 responses, accentuating interleukin (IL)-4 secretion by Th2 cel ls. Elevated prostaglandin E(2) secretion correlates with abnormally i ncreased cyclic adenosine monophosphate-phosphodiesterase activity in monocytes and this, along with other defective inflammatory cell respo nses, can be normalized in vitro by phosphodiesterase inhibitors, It a ppears that in addition to prostaglandin E(2), IL-10 acts to regulate the balance between Th1 and Th2 functional responses accounting for ma ny atopic features, including increased IL-4, IL-5, and IL-6 productio n by T cells; increased IgE synthesis; decreased interferon-gamma prod uction; and impaired cell-mediated immune responses, All of these abno rmalities can be related to increased phosphodiesterase activity in at opic monocytes, and inhibition of this key enzyme appears to reverse a topic dermatitis inflammatory abnormalities in vitro and in vivo.