Role of acute-phase proteins in interleukin-1-induced nonspecific resistance to bacterial infections in mice

M. T E Vogels, L. Cantoni, M. Carelli, M. Sironi, P. Ghezzi, J. W M Van der Meer

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Abstract

Treatment with a single low dose (80 to 800 ng) of interleukin-1 (IL-1) 24 h before a lethal bacterial challenge of granulocytopenic and normal mice enhances nonspecific resistance. Since IL-1 induces secretion of acute-phase proteins, liver proteins which possess several detoxifying effects, we investigated the role of these proteins in the IL-1 induced protection. Inhibition of liver protein synthesis with D-galactosamine (GALN) completely inhibited the IL-1-induced synthesis of acute-phase proteins. GALN pretreatment abolished the protective effect of IL-1 on survival completely (neutropenic mice infected with Pseudomonas aeruginosa) or partially (nonneutropenic mice infected with Klebsiella pneumoniae). Pretreatment with IL-6, a cytokine induced by IL-1, did not reproduce the protection offered after IL-1 pretreatment, nor did it enhance or deteriorate the IL-1-enhanced resistance to infection. A protective effect of IL-1 via effects on glucose homeostasis during the acute-phase response was investigated by comparing plasma glucose levels in IL-1-treated mice and control mice before and during infection. Although glucose levels in IL-1-pretreated mice were somewhat higher in the later stages of infection, no significant differences from levels in control mice were present, and the glucose levels in control- treated animals never fell to hypoglycemic values. We conclude that the IL- 1-induced nonspecific resistance is mediated neither by the induction of IL- 6 nor by the effects of IL-1 on glucose homeostasis. Acute-phase proteins generated after IL-1 pretreatment, however, seem to play a critical role in the IL-1-induced protection to infection.

Original languageEnglish
Pages (from-to)2527-2533
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume37
Issue number12
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Pharmacology (medical)

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    Vogels, M. T. E., Cantoni, L., Carelli, M., Sironi, M., Ghezzi, P., & Van der Meer, J. W. M. (1993). Role of acute-phase proteins in interleukin-1-induced nonspecific resistance to bacterial infections in mice. Antimicrobial Agents and Chemotherapy, 37(12), 2527-2533.