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IL-1 receptor–type expression in relation to atopy

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1 IL-1 receptor–type expression in relation to atopy
Kirtibala Gupta, MSc, Againdra Bewtra, MD  Journal of Allergy and Clinical Immunology  Volume 103, Issue 6, Pages (June 1999) DOI: /S (99) Copyright © 1999 Mosby, Inc. Terms and Conditions

2 Fig. 1 Role of IL-1. Thick arrows, Synthesis and secretion; thin arrows, action; (+), upregulation; (–), downregulation. PAF, Platelet-activating factor. Journal of Allergy and Clinical Immunology  , DOI: ( /S (99) ) Copyright © 1999 Mosby, Inc. Terms and Conditions

3 Fig. 2 IL-1 has 2 receptors, IL-1RI and IL-1RII. Both types have membrane (mIL-1R) and soluble (sIL-1R) forms. mIL-1RI is the active receptor because it has a signal transduction mechanism associated with it. mIL-1RII is the decoy receptor because it has no signal transducing capability. sIL-1RI and sIL-1RII are soluble receptors with no signal transduction mechanisms, and thus they act as mops for IL-1. Journal of Allergy and Clinical Immunology  , DOI: ( /S (99) ) Copyright © 1999 Mosby, Inc. Terms and Conditions

4 Fig. 3 IL-1β secreted by cultured PBMCs from 6 nonatopic (open bars) and 8 atopic donors (filled bars) into the supernatant was measured in triplicate with ELISA and is represented as means ± SD. PBMCs were cultured for 24 hours with PHA (stimulated cells) or without PHA (unstimulated cells) . *, Statistical significance between atopic and nonatopic individuals (unstimulated state, P < .05); #, statistical significance between unstimulated and stimulated states (atopic donors, P < .005; nonatopic donors, P < .005). Journal of Allergy and Clinical Immunology  , DOI: ( /S (99) ) Copyright © 1999 Mosby, Inc. Terms and Conditions

5 Fig. 4 Membrane IL-1 receptors type I (A ) and type II (B ) PBLs were measured in triplicate with ELISA, and concentrations were determined as detailed in the Methods section. PBLs isolated from 12 nonatopic and 8 atopic donors were stimulated with PHA and cultured for 24 hours. Open bars represent receptors expressed on PBLs from atopic donors, and filled bars represent mIL-1Rs expressed on PBLs from atopic donors. Data are represented as means ± SD. *, Statistical significance of mIL-1R expression by PBLs from atopic and nonatopic persons (mIL-1RI, P < .0001; mIL-1RII, P < .05). Journal of Allergy and Clinical Immunology  , DOI: ( /S (99) ) Copyright © 1999 Mosby, Inc. Terms and Conditions

6 Fig. 5 Sera sIL-1RI and sIL-1RII obtained from 12 nonatopic (open bars) and 8 atopic donors (filled bars) were measured with ELISA in triplicate. Values denoted are mean concentrations ± SD. *, Statistical significance between atopic and nonatopic persons (sIL-1RI, P < .0001; sIL-1RII, P < .0001). Journal of Allergy and Clinical Immunology  , DOI: ( /S (99) ) Copyright © 1999 Mosby, Inc. Terms and Conditions

7 Fig. 6 Soluble IL-1 receptor type I (A ) and type II (B ) levels in supernatants of cultured PBMCs from atopic (n = 8; filled bars ) and nonatopic (n = 12; open bars ) subjects were determined in triplicate. PBMCs were cultured for 24 hours with PHA (stimulated PBMC) and without PHA (unstimulated PBMC) , and values are represented as means ± SD. *, Statistical significance between atopic and nonatopic individuals (sIL-1RI levels in unstimulated and stimulated state, P < .001); #, statistical significance between unstimulated and stimulated states (sIL-1RI in atopic donors, P < .005; nonatopic donors, P < .05; sIL-1RII in nonatopic donors, P < .01). Journal of Allergy and Clinical Immunology  , DOI: ( /S (99) ) Copyright © 1999 Mosby, Inc. Terms and Conditions

8 Fig. 7 The 2 panels illustrate our results of atopic and nonatopic individuals. We found similar concentrations of IL-1β in both donors but higher numbers of mIL-1Rs on PBLs of atopic donors. We also found higher concentrations of both soluble receptors in the circulation and cultured PBL supernatants of nonatopic donors. Thus there is an increased tendency of IL-1β binding to mIL-1Rs in an atopic individual, leading to signal transduction and an inflammatory response. In nonatopic subjects there is a higher tendency of IL1β binding to sIL-1Rs, which therefore results in no inflammatory response. Journal of Allergy and Clinical Immunology  , DOI: ( /S (99) ) Copyright © 1999 Mosby, Inc. Terms and Conditions

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