Prolactin triggers pro-inflammatory immune responses in peripheral immune cells.
The peptide hormone prolactin (PRL) is produced by specialized cells in the anterior pituitary gland and in a number of sites outside the pituitary. Its biological actions consist of various roles in reproduction, lactation, and of a number of homeostatic biological activities that also include immune functions. Elevated serum PRL concentrations often correlate with abnormalities in immune responses. To determine the influence of PRL on human immune cells, human whole blood cultures were stimulated with lipopolysaccharide (LPS), supplemented with various concentrations of human recombinant PRL. We found that PRL, at concentrations achievable during pregnancy, anesthesia and medication, significantly amplified interleukin (IL)-12 and tumor necrosis factor-alpha (TNF-alpha) synthesis in LPS-stimulated cultures, in a dose-dependent manner. Conversely, synthesis of the anti-inflammatory cytokine IL-10 only increased significantly at very high concentrations of supplemented PRL. PRL alone was not able to induce any measurable secretion of TNF-alpha, IL-10, or IL-12 in non-stimulated, whole blood cultures. However, we demonstrated that PRL, by itself or in combination with LPS, causes an increase in the binding activity of the transcription factors nuclear factor-kappaB (NFkappaB) and interferon regulatory factor-1 (IRF-1), which are known to promote TNF-alpha and IL-12 secretion. These data suggest that PRL promotes pro-inflammatory immune responses via NFkappaB and IRF-1, which may affect pathophysiological processes in physiological hyperprolactinemic states.
Brand
Jörg-Matthias
JM
Institute of Immunology and Transfusion Medicine, University of Lübeck, Germany. brand@immu.mu-luebeck.de
Frohn
Christoph
C
Cziupka
Katharina
K
Brockmann
Christian
C
Kirchner
Holger
H
Luhm
Jürgen
J
D001773:Blood Cells / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D006966:Hyperprolactinemia / Q000276:immunology; D007109:Immunity / Q000502:physiology; D007249:Inflammation / Q000276:immunology; D050856:Interferon Regulatory Factor-1; D007774:Lactation / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D011388:Prolactin / Q000494:pharmacology / Q000502:physiology*; D012098:Reproduction / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
D016207:Cytokines; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010750:Phosphoproteins; D011388:Prolactin