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Acute phase levels of C-reactive protein enhance IL-1 beta and IL-1ra production by human blood monocytes but inhibit IL-1 beta and IL-1ra production by alveolar macrophages.

C A Pue, R F Mortensen, C B Marsh, H A Pope and M D Wewers
J Immunol February 15, 1996, 156 (4) 1594-1600;
C A Pue
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R F Mortensen
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C B Marsh
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H A Pope
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M D Wewers
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Abstract

C-reactive protein (CRP), the major acute phase protein in humans, was purified free of endotoxin (LPS) (< 10 pg of LPS/mg of purified CRP) and evaluated for its ability to modulate LPS-induced production of IL-1 beta and IL-1 receptor antagonist (IL-1ra) from human PBMC and lung macrophages. PBMC (5 x 10(6)/ml) released low levels of IL-1 beta in response to either CRP (250 micrograms/ml) or LPS (100 ng/ml) for 18 h (0.3 +/- 0.1 and 1.5 +/- 0.7 ng/ml, respectively). However, when CRP (250 micrograms/ml) and LPS (100 ng/ml) were combined, PBMC released 9.7 +/- 2.9 ng/ml (p < 0.001 vs LPS alone). This synergy was removed by immunodepletion of CRP before stimulation. With respect to IL-1ra, although CRP induced IL-1ra production from PBMC (0.8 +/- 0.3 ng/ml control, 2.6 +/- 1.3 ng/ml with CRP), CRP did not synergize with LPS for IL-1ra production (15.0 +/- 0.7 ng/ml LPS alone vs 15.4 +/- 1.4 ng/ml LPS and CRP). In contrast, lung macrophages responded to CRP quite differently than PBMC. Macrophages (10(6)/ml) were not stimulated to produce IL-1 beta or IL-1ra by CRP alone. When combined with LPS, CRP inhibited IL-1 beta and IL-1ra release induced by LPS (for IL-1 beta release, LPS induced 3.0 +/- 1.7 ng/ml vs 1.1 +/- 0.4 for combined LPS and CRP; for IL-1ra release, LPS induced 12.9 +/- 2.3 ng/ml vs 7.6 +/- 2.3 ng/ml for combined LPS and CRP). These data suggest that acute phase levels of CRP may have divergent effects depending on the target population. CRP may be largely proinflammatory to blood monocytes responding to LPS since IL-1 beta production is augmented over IL-1ra production. However, in tissue compartments the effects of CRP may be largely immunosuppressive to LPS-induced tissue macrophage IL-1 beta production.

  • Copyright © 1996 by American Association of Immunologists

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The Journal of Immunology
Vol. 156, Issue 4
15 Feb 1996
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Acute phase levels of C-reactive protein enhance IL-1 beta and IL-1ra production by human blood monocytes but inhibit IL-1 beta and IL-1ra production by alveolar macrophages.
C A Pue, R F Mortensen, C B Marsh, H A Pope, M D Wewers
The Journal of Immunology February 15, 1996, 156 (4) 1594-1600;

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Acute phase levels of C-reactive protein enhance IL-1 beta and IL-1ra production by human blood monocytes but inhibit IL-1 beta and IL-1ra production by alveolar macrophages.
C A Pue, R F Mortensen, C B Marsh, H A Pope, M D Wewers
The Journal of Immunology February 15, 1996, 156 (4) 1594-1600;
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Print ISSN 0022-1767        Online ISSN 1550-6606