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Clin. Vaccine Immunol. doi:10.1128/CVI.00289-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Longitudinal tracking of cytokine patterns after acute exposure to tuberculosis in household contacts. Distinct patterns of IFN/IL10 ratios are associated with protection and disease development

Department of Pathology and Microbiology, Aga Khan University, Stadium Road, P.O.Box 3500, Karachi-74800, Pakistan; Masoomeen General Hospital, Musa Lane, Kharadar, Karachi, Pakistan

^* To whom correspondence should be addressed. Email: rabia.hussain{at}aku.edu.

	Abstract

Household contacts (HC) of tuberculosis (TB) patients are at higher risk of infection as well as developing active disease. Longitudinal tracking of antigen specific cytokines after acute exposure may significantly advance our understanding of dynamic changes in cytokine patterns associated with disease establishment. To achieve this objective, we carried out a prospective cohort study of healthy HC post TB exposure. Cytokine patterns (IFN and IL10) at 0, 6, 12 and 24 months were assessed in response to mycobacterial antigens (CF) and non specific mitogens (PHA and LPS). Seven out of 109 (6.4%) HC developed active disease in 6/7 females, which occurred between 12-15 months in 5/20 families. The most significant findings was, the exponential increase (1000-fold) in both CF and PHA/LPS induced IFN/IL10 ratio in healthy HC (N=26), which peaked at 12 months, compared to HC who developed disease (N=7) in whom a relatively flat response was observed during the 24-month period. Linear trends for 0-12 and 0-24 months for CF induced IFN/IL10 ratio showed significant differences between the two groups using Mantel extension test for square analysis (OR 0.45; CI 0.295-0.685; p= 0.0002). Our results strongly suggest that the magnitude of IFN/IL10 ratio post exposure at 12 months may be a critical determinant in resolution of infection. These studies provide new insights with respect to cytokine responses associated with disease establishment or resolution of infection after natural exposure in tuberculosis and have implications for TB control programs as well vaccine efficacy studies.