Pd. Rogers et al., Amphotericin B-induced interleukin-1 beta expression in human monocytic cells is calcium and calmodulin dependent, J INFEC DIS, 180(4), 1999, pp. 1259-1266
Amphotericin B remains the agent of choice for treatment of severe fungal i
nfections. Its use is hindered by adverse effects, including infusion-relat
ed fever, chills, and hypotension, as well as nephrotoxicity with secondary
anemia, hypokalemia, and hypomagnesemia. Amphotericin B-induced transcript
ion and expression of interleukin (IL)-1 beta by human monocytes is believe
d to be involved in mediating infusion-related adverse effects. It is shown
here that agents that increase intracellular calcium [Ca++](i) (A23187 and
thapsigargin) in human monocytic cells also induce IL-1 beta expression. F
urthermore, amphotericin B-induced IL-1 beta expression is attenuated by th
e calmodulin antagonist calmidazolium, Amphotericin B 5.41 mu M increases [
Ca++](i) by up to 300 nM in these cells, In the presence of a nominal calci
um buffer or EGTA, amphotericin B-induced IL-1 beta expression is attenuate
d. Thus, amphotericin B acts as an ionophore to increase [Ca++](i) and acti
vates calmodulin-mediated expression of IL-1 beta in human monocytes.