Regulation of murine macrophage IL-12 production

Activation of macrophages in vivo, restimulation in vitro, and modulation by other cytokines

Marianne J. Skeen, Mark Miller, Thomas M. Shinnick, Harry Kirk Ziegler

Research output: Contribution to journalArticle

209 Citations (Scopus)

Abstract

IL-12 is important in the host response to a variety of pathogens. It plays an adjuvant-like role in an initial immune response as well as a therapeutic role in established infections. Despite its well documented importance, comparatively little is known about the regulation of IL-12 production. In this study, we examined IL-12 production by cultured murine peritoneal macrophages from two perspectives: 1) macrophage activation in vivo, and 2) stimulation of IL-12 secretion in vitro. Macrophages were maximally activated within 48 h in vivo during infection with Listeria. Interestingly, although avirulent or heat-killed Listeria induced only minimal production of IL-12 by macrophages, the immunogenic combination of heat-killed bacteria and rIL-12 was highly stimulatory for IL-12 production. LPS and peritoneal inflammatory agents were also stimulatory, but latex heads were ineffective, indicating that microbial components were essential and phagocytosis alone was insufficient. Restimulation in vitro revealed similar patterns, in that infection and LPS were stimulatory but latex beads were not. A systematic survey of potential stimulatory agents showed that microbial heat shock proteins, crude bacterial extracts, bacterial superantigens, a yeast extract, and dsRNA induced IL-12 in vitro. Other cytokines also influenced IL-12 induction. IFN-γ, which is up-regulated during infection, acted in synergy with other stimuli, suggesting an amplification loop for IL-12 production, whereas IL-4, IL-10, IL-13, and TGF- β were inhibitory. The existence of a broad range of stimuli from a wide variety of pathogenic organisms underscores the fundamental importance of IL- 12 in host defense.

Original languageEnglish (US)
Pages (from-to)1196-1206
Number of pages11
JournalJournal of Immunology
Volume156
Issue number3
StatePublished - Feb 1 1996

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Macrophage Activation
Interleukin-12
Macrophages
Cytokines
Hot Temperature
Infection
In Vitro Techniques
Superantigens
Listeriosis
Listeria
Interleukin-13
Latex
Peritoneal Macrophages
Heat-Shock Proteins
Complex Mixtures
Microspheres
Phagocytosis
Interleukin-4
Interleukin-10
Yeasts

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Regulation of murine macrophage IL-12 production : Activation of macrophages in vivo, restimulation in vitro, and modulation by other cytokines. / Skeen, Marianne J.; Miller, Mark; Shinnick, Thomas M.; Kirk Ziegler, Harry.

In: Journal of Immunology, Vol. 156, No. 3, 01.02.1996, p. 1196-1206.

Research output: Contribution to journalArticle

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