Effects of prolactin and metoclopramide on macrophage cytokine gene expression in late sepsis

Xiao Hong Zhu, René Zellweger, Matthias W. Wichmann, Alfred Ayala, Irshad H. Chaudry

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

Previous studies indicate a profound suppression of tumour necrosis factor alpha (TNF-α), IL-1β and IL-6 release capacity by peritoneal macrophage (PMΦ), splenic macrophage (SMΦ) and Kupffer cells (KC) during late sepsis. Such a loss of functional capacity may reduce the animal's ability to ward off infection. Prolactin is known to enhance monocyte, T- and B-lymphocyte immune responses under normal conditions and has beneficial effects on cell-mediated immunity after haemorrhage. In this respect, the dopamine antagonist, metoclopramide, has been reported to increase circulating prolactin levels. Nonetheless, it remains unknown whether prolactin or metoclopramide have any salutary effect on macrophage (MΦ) cytokine gene expression following sepsis. To study this, male C3H/HeN mice were subjected to sepsis and immediately thereafter were treated with prolactin (100 μg/25 g body weight, s.c.), metoclopramide (100 μg/100 g BW, s.c.) or given saline. PMΦ, SMΦ and KC (only SMΦ and KC in metoclopramide-treated animals) were isolated at 24 h after sepsis. The monolayers were stimulated with or without LPS 10 μg/ml for 1 h in vitro. Total RNA was extracted and mRNA was detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). A significant depression of constitutive and inducible mRNA levels of IL-1β, IL-6 and TNF-α in all three MΦ populations were observed, when compared with shams (with exception of KC IL-6 mRNA in unstimulated cells). Prolactin as well as metoclopramide treatment after the onset of sepsis caused significant elevation of constitutive and inducible cytokine gene expression in all macrophages examined. Thus, prolactin and metoclopramide enhance the depressed MΦ gene expression and may be useful in improving cell-mediated immunity during sepsis.

Original languageEnglish
Pages (from-to)437-446
Number of pages10
JournalCytokine
Volume9
Issue number6
DOIs
Publication statusPublished - Jun 1997
Externally publishedYes

Keywords

  • Cytokine gene expression
  • Kupffer cells
  • Metoclopramide
  • Peritoneal macrophages
  • Prolactin
  • Sepsis
  • Splenic macrophages

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