Natural measles causes prolonged suppression of interleukin-12 production

Among vaccine-preventable diseases, measles is the preeminent killer of chi ldren worldwide. Infection with measles virus (MV) is associated with prolo nged suppression of cell-mediated immune responses, a phenomenon that is th ought to underlie the susceptibility to secondary infections that accounts for most measles-related mortality. Interleukin (IL)-12 is critical for the orchestration of cellular immunity. MV specifically ablates IL-12 producti on by monocyte/macrophages in vitro through binding to CD46, a complement r egulatory protein that is an MV receptor. To address the effect of MV on IL -12 responses in vivo, cytokine production was examined in Gambian patients with measles. IL-12 production by peripheral blood monocytes from such pat ients is markedly suppressed, which provides a unifying mechanism for many of the immunologic abnormalities associated with measles. This suppression is prolonged, with significant, stimulus-specific inhibition of IL-12 produ ction demonstrable months after recovery from acute infection. However, des pite this suppression, IL-12 responsiveness remains intact.