Amphotericin B-induced interleukin-1β expression in human monocytic cells is calcium and calmodulin dependent

Phillip Rogers, Robert E. Kramer, Stanley W. Chapman, John D. Cleary

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Amphotericin B remains the agent of choice for treatment of severe fungal infections. Its use is hindered by adverse effects, including infusion-related fever, chills, and hypotension, as well as nephrotoxicity with secondary anemia, hypokalemia, and hypomagnesemia. Amphotericin B- induced transcription and expression of interleukin (IL)-1β by human monocytes is believed 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-1β expression. Furthermore, amphotericin B-induced IL-1β expression is attenuated by the calmodulin antagonist calmidazolium. Amphotericin B 5.41 μM increases [Ca++](i) by up to 300 nM in these cells. In the presence of a nominal calcium buffer or EGTA, amphotericin B-induced IL-1β expression is attenuated. Thus, amphotericin B acts as an ionophore to increase [Ca++](i) and activates calmodulin-mediated expression of IL-1β in human monocytes.

Original languageEnglish (US)
Pages (from-to)1259-1266
Number of pages8
JournalJournal of Infectious Diseases
Volume180
Issue number4
DOIs
StatePublished - Dec 1 1999

Fingerprint

Amphotericin B
Calmodulin
Interleukin-1
Calcium
calmidazolium
Monocytes
Chills
Thapsigargin
Hypokalemia
Mycoses
Egtazic Acid
Ionophores
Calcimycin
Hypotension
Anemia
Buffers
Fever

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Amphotericin B-induced interleukin-1β expression in human monocytic cells is calcium and calmodulin dependent. / Rogers, Phillip; Kramer, Robert E.; Chapman, Stanley W.; Cleary, John D.

In: Journal of Infectious Diseases, Vol. 180, No. 4, 01.12.1999, p. 1259-1266.

Research output: Contribution to journalArticle

Rogers, Phillip ; Kramer, Robert E. ; Chapman, Stanley W. ; Cleary, John D. / Amphotericin B-induced interleukin-1β expression in human monocytic cells is calcium and calmodulin dependent. In: Journal of Infectious Diseases. 1999 ; Vol. 180, No. 4. pp. 1259-1266.
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