Endothelial activation and subclinical microvascular occlusions are an ongoing process during steady-state sickle cell disease, leading to interleukin production and an acute-phase response. Alpha-2-macroglobulin (α2M) is an acute-phase protein mainly regulated by interleukin-6 (IL-6). On the other hand, α2M acts as a carrier protein for IL-6 during inflammatory stress. The purpose of this study is to further assess the interactions between IL-6 and α2M as potent modulators of inflammatory reactions during the steady state of sickle cell disease. We measured α2M and IL-6 levels in 21 patients (12 male, 9 female; age range 12–44 years) in the steady state of sickle cell disease. Four patients had homozygous sickle cell anaemia and 17 had double heterozygous sickle cell/β-thalassaemia. Diagnostic quantification of α2M was performed by rate nephelometry. Commercial enzyme immunoassay test kits were used for the quantitative measurement of IL-6. The α2M and IL-6 levels were compared to the values obtained from healthy volunteers. Mean values (± SD) of α2M and IL-6 were found to be significantly increased (p < 0.0005) in the patients (α2M: 337.2 ± 104 mg/dl; IL-6: 4 ± 2.1 pg/ml) compared to the healthy controls (α2M: 204.2 ± 45.8 mg/dl; IL-6: 1.15 ± 2.5 pg/ml). IL-6 values were positively correlated with α2M levels (r = 0.61, p < 0.01). We observed increased α2M and IL-6 levels in steady-state sickle cell disease and a positive correlation between these two inflammatory mediators. We suggest that α2M is a potent modulator of the inflammatory reaction and tissue repair mechanism during steady-state microvascular occlusions. Elucidating the role of α2M in sickle cell disease could lead to the development of novel strategies and therapies for preventing the harmful systemic or local effects of excess cytokine production.

Keywords:
Alpha-2-macroglobulin, Interleukin-6, Sickle cell disease
© 2001 S. Karger AG, Basel
2001
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.