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Cytokine Production Is Altered in Monocytes from Children with Hemolytic Uremic Syndrome

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Abstract

Purpose

The interaction of Shiga toxin (Stx) and/or lipopolysaccharide (LPS) with monocytes (Mo) may be central to the pathogenesis of hemolytic uremic syndrome (HUS), providing the cytokines necessary to sensitize endothelial cells to Stx action. We have previously demonstrated phenotypical alterations in Mo from HUS patients, including increased number of CD16+ Mo. Our aim was to investigate cytokine production in Mo from HUS patients.

Methods

We evaluated TNF-α and IL-10 intracellular contents and secretion in the different Mo subsets in mild (HUS 1) and moderate/severe (HUS 2 + 3) patients. As controls, we studied healthy (HC) and infected children (IC). We also studied Mo responsive capacity towards LPS, measuring the modulation of Mo surface molecules and cytokine production.

Results

In basal conditions, the intracellular measurement of TNF-α and IL-10 revealed that the highest number of cytokine-producing Mo was found in HUS 2 + 3 and IC, whereas LPS caused a similar increase in TNF-α and IL-10-producing Mo for all groups. However, when evaluating the release of TNF-α and IL-10, we found a diminished secretion capacity in the entire HUS group and IC compared to HC in basal and LPS conditions. Similarly, a lower Mo response to LPS in HUS 2 + 3 and IC groups was observed when surface markers were studied.

Conclusion

These results indicate that Mo from severe cases of HUS, similar to IC but different to mild HUS cases, present functional changes in Mo subpopulations and abnormal responses to LPS.

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Acknowledgements

This investigation was supported by Agencia Nacional de Promoción Científica y Tecnológica, CONICET, and Fundación “Alberto J. Roemmers”, Argentina. The authors thank Marta Felippo, Nora Galassi, and Norma Riera for their excellent technical assistance. The authors also thank Fundación de la Hemofilia and Academia Nacional de Medicina for the use of the FACScan flow cytometer.

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Authors and Affiliations

  1. Immunology Department, Academia Nacional de Medicina, Pacheco de Melo 3081, C1425AUM, Buenos Aires, Argentina

    Gabriela C. Fernández, María V. Ramos, Veronica I. Landoni, Leticia V. Bentancor, Romina J. Fernández-Brando, Martín A. Isturiz & Marina S. Palermo

  2. Nephrology Department, Pediatric Municipal Hospital, San Justo, Buenos Aires, Argentina

    Ramón Exeni, María del Carmen Laso, Andrea Exeni & Irene Grimoldi

  3. Instituto de Medicina Experimental (IMEX) CONICET, Buenos Aires, Argentina

    Gabriela C. Fernández, María V. Ramos, Veronica I. Landoni, Leticia V. Bentancor, Romina J. Fernández-Brando, Martín A. Isturiz & Marina S. Palermo

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  1. Gabriela C. Fernández
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  2. María V. Ramos
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  3. Veronica I. Landoni
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  6. Ramón Exeni
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  7. María del Carmen Laso
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  8. Andrea Exeni
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Correspondence to Gabriela C. Fernández.

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Fernández, G.C., Ramos, M.V., Landoni, V.I. et al. Cytokine Production Is Altered in Monocytes from Children with Hemolytic Uremic Syndrome. J Clin Immunol 32, 622–631 (2012). https://doi.org/10.1007/s10875-011-9646-z

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  • DOI: https://doi.org/10.1007/s10875-011-9646-z

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