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Infection and Immunity, June 2005, p. 3301-3306, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3301-3306.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Skin Test Performed with Highly Purified Mycobacterium tuberculosis Recombinant Protein Triggers Tuberculin Shock in Infected Guinea Pigs

Stephen T. Reece,1 Nicole Stride,1 Pamela Ovendale,2 Steven G. Reed,1 and Antonio Campos-Neto3*

Infectious Disease Research Institute, Seattle, Washington,1 Corixa Corporation, Seattle, Washington,2 The Forsyth Institute, Boston, Massachusetts3

Received 14 December 2004/ Returned for modification 14 January 2005/ Accepted 27 January 2005

Tuberculin shock due to inoculation of Mycobacterium tuberculosis antigens in patients with tuberculosis is a serious syndrome originally described over 100 years ago by Robert Koch. Here, we present experimental evidence that a single M. tuberculosis recombinant protein, CFP-10, triggers this syndrome. Intradermal inoculation of CFP-10 elicits in M. tuberculosis-infected mice high levels of serum tumor necrosis factor alpha and causes tuberculin shock in infected guinea pigs characterized by hypothermia and death within 6 to 48 h after the antigen inoculation. Autopsies of these animals revealed intense polycythemia and hemorrhagic patches in the lung parenchyma, a pathological observation consistent with tuberculin shock. These results point to the possible occurrence of tuberculin shock in sensitive individuals inoculated with highly purified M. tuberculosis recombinant proteins as vaccine candidates or skin test reagents.

* Corresponding author. Mailing address: The Forsyth Institute, 140 The Fenway, Boston, MA 02115. Phone: (617) 262-5200. Fax: (617) 892-8326. E-mail: acampos{at}forsyth.org.

Editor: J. L. Flynn

Infection and Immunity, June 2005, p. 3301-3306, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3301-3306.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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