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Infection and Immunity, September 2000, p. 5393-5400, Vol. 68, No. 9
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Distinct Response Kinetics of Gamma Interferon and Interleukin-4 in Bovine Tuberculosis

S. G. Rhodes,1,* N. Palmer,2 S. P. Graham,3 A. E. Bianco,3 R. G. Hewinson,1 and H. M. Vordermeier1

TB Research Group1 and TB Diagnostics Laboratory,2 Veterinary Laboratories Agency, Addlestone, Surrey KT15 3NB, and Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA,3 United Kingdom

Received 9 March 2000/Returned for modification 7 April 2000/Accepted 14 June 2000

This study shows that gamma interferon (IFN-gamma ) and interleukin-4 (IL-4) cytokine responses are produced by peripheral blood cells in cattle infected with Mycobacterium bovis. The different kinetics of the IFN-gamma and IL-4 responses to bovine tuberculin and to ESAT-6 following experimental intratracheal infection with M. bovis are described. An early increase in IFN-gamma was observed that was maintained throughout the period studied. In contrast, the IL-4 response was delayed and confined to a peak of activity lasting 6 to 8 weeks. Interestingly, an experimental challenge of cattle with a lower dose of M. bovis which did not result in the development of lesions, positive DTH skin test, or substantial IFN-gamma responses nevertheless generated strong specific IL-4 responses. Investigation of naturally infected M. bovis field reactors showed increased IFN-gamma and IL-4 responses compared to uninfected cattle and that both of these cytokines were equally able to differentiate infected from uninfected animals. The magnitude of the M. bovis-induced IL-4 responses were found to be similar to the antigen-specific IL-4 responses of cattle infected with the parasitic nematode Onchocerca ochengi, further supporting the presence of this type 2 cytokine in bovine tuberculosis.

* Corresponding author. Mailing address: VLA, Addlestone, Surrey KT15 3NB, United Kingdom. Phone: 01932-357506. Fax: 01932-357684. E-mail: srhodes.vla{at}gtnet.gov.uk.

Infection and Immunity, September 2000, p. 5393-5400, Vol. 68, No. 9
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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