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Infection and Immunity, March 2004, p. 1807-1811, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1807-1811.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Mycobacterial Purified Protein Derivatives Stimulate Innate Immunity: Malawians Show Enhanced Tumor Necrosis Factor Alpha, Interleukin-1ß (IL-1ß), and IL-10 Responses Compared to Those of Adolescents in the United Kingdom

Rosemary E. Weir,1,{dagger} Gillian F. Black,1,2,{dagger} Hazel M. Dockrell,1 Sian Floyd,1 Paul E. M. Fine,1,2 Steven D. Chaguluka,2 Sally Stenson,1 Elizabeth King,1 Bernadette Nazareth,3 David K. Warndorff,2 Bagrey Ngwira,2 Amelia C. Crampin,1,2 Lorren Mwaungulu,2 Lifted Sichali,2 Elizabeth Jarman,2 Linda Donovan,2 and Jenefer M. Blackwell4*

Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London,1 Redbridge and Waltham Forest Health Authority, Ilford,3 Cambridge Institute for Medical Research, Cambridge, United Kingdom,4 Karonga Prevention Study, Chilumba, Malawi2

Received 6 August 2003/ Returned for modification 22 September 2003/ Accepted 1 December 2003

To investigate the role of innate immunity in variable efficacy of Mycobacterium bovis BCG vaccination in Malawi and the United Kingdom, we examined 24-h tumor necrosis factor alpha, interleukin-1ß (IL-1ß), and IL-10 responses to mycobacterial purified protein derivatives (PPDs). The rank order in stimulatory potency for different PPDs was the same for all three cytokines. Before vaccination Malawians made higher pro- and anti-inflammatory responses than did United Kingdom subjects. Fewer than 5% of United Kingdom subjects made IL-10 in response to any PPD, compared to 19 to 57% responders among Malawians. Priming for regulatory IL-10 may contribute to the smaller increase in gamma interferon responses in Malawians compared to United Kingdom subjects following BCG vaccination.

* Corresponding author. Mailing address: Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital Site, Hills Road, Cambridge CB2 2XY, United Kingdom. Phone: 44 1223 336947. Fax: 44 1223 331206. E-mail: jennie.blackwell{at}cimr.cam.ac.uk.

Editor: A. D. O'Brien

{dagger} R.E.W. and G.F.B. contributed equally to this work.

Infection and Immunity, March 2004, p. 1807-1811, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1807-1811.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.





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