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Infection and Immunity, September 2005, p. 6101-6109, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.6101-6109.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Therapeutic Efficacy of High-Dose Intravenous Immunoglobulin in Mycobacterium tuberculosis Infection in Mice

Eleanor Roy,1,{dagger} Evangelos Stavropoulos,1,{dagger} John Brennan,1 Stephen Coade,1 Elena Grigorieva,2 Barry Walker,3 Belinda Dagg,3 Ricardo E. Tascon,1 Douglas B. Lowrie,1 M. Joseph Colston,1 and Stephen Jolles1,4*

Divisions of Mycobacterial Research,1 Developmental Neurobiology, National Institute for Medical Research, Mill Hill, London, United Kingdom,2 National Institute for Biological Standards and Control, Hertfordshire, United Kingdom,3 Department of Clinical Immunology, Royal Free Hospital, London, United Kingdom4

Received 27 February 2005/ Returned for modification 19 April 2005/ Accepted 9 May 2005

Intravenous immunoglobulin (IVIg) is used to treat patients with primary antibody deficiencies and, at high doses, to treat a range of autoimmune and inflammatory disorders. With high-dose IVIg (hdIVIg), immunomodulatory mechanisms act on a range of cells, including T cells, B cells, and dendritic cells. Here, we demonstrate that the treatment of M. tuberculosis-infected mice with a single cycle of hdIVIg resulted in substantially reduced bacterial loads in the spleen and lungs when administered at either an early or late stage of infection. Titration of the IVIg showed a clear dose-response effect. There was no reduction in bacterial load when mice were given equimolar doses of another human protein, human serum albumin, or maltose, the stabilizing agent in the IVIg preparation. HdIVIg in vitro had no inhibitory effect on the growth of M. tuberculosis in murine bone marrow-derived macrophages. In addition, the effect of hdIVIg on bacterial loads was not observed in nude mice, suggesting the involvement of conventional T cells. Analysis of T cells infiltrating the lungs revealed only small increases in CD8+ but not CD4+ T-cell numbers in hdIVIg-treated mice. The mechanism of action of hdIVIg against tuberculosis in mice remains to be determined. Nevertheless, since hdIVIg is already widely used clinically, the magnitude and long duration of the therapeutic effect seen here suggest that IVIg, or components of it, may find ready application as an adjunct to therapy of human tuberculosis.

* Corresponding author. Mailing address: Division of Mycobacterial Research, National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom. Phone: 0208 959 3666. Fax: 0208 816 2571. E-mail: sjolles{at}nimr.mrc.ac.uk.

Editor: J. L. Flynn

{dagger} Both authors contributed equally.

Infection and Immunity, September 2005, p. 6101-6109, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.6101-6109.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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  • Yew, W. W., Leung, C. C. (2006). Update in tuberculosis 2005.. Am. J. Respir. Crit. Care Med. 173: 491-498 [Full Text]  


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