title: Interferon gamma/IL10 ratio defines the disease severity in pulmonary and extra pulmonary tuberculosis.
abstract: Several cytokines (IFN gamma, TNF alpha, IL10 and IL6) show an association with either disease localization or dissemination in tuberculosis. There are also reports of involvement of extra-pulmonary sites in tuberculosis with differential clinical severity. However, no comparative study of biomarkers across the disease severity spectrum is available. This was the purpose of the current study. Cytokines (IFN gamma, TNFalpha, IL10 and IL6) secreted in response to a panel of stimulants (PHA, LPS or mycobacterial antigens) in whole blood were determined in eighty-two tuberculosis patients. WHO criteria was applied for stratification of patients according to disease severity: disseminated and or severe disease (EPTB1; N=29); disease localized to lung parenchyma (PTB; N=32) and disease localized to peripheral sites without lung involvement (EPTB2; N=21). Mycobacterial antigens induced IFN gamma/IL10 ratio showed a direct relationship with disease severity ranking (median ratios: EPTB1=0.21; PTB=0.85; EPTB2=7.7) and the highest correlation (Spearman Rank; rho=0.673, p<0.000001). IFN gamma/IL10 ratio also rank ordered clinical severity as it relates to anatomic sites. IFN gamma/IL10 ratio may therefore provide a useful objective marker of disease severity in both pulmonary and extra-pulmonary tuberculosis.
authors.affiliation: Department of Pathology, Aga Khan University, Stadium Road, PO Box 3500, Karachi 74800, Pakistan.
authors.forename: Bushra
authors.initials: B
authors.lastname: Jamil
authors.forename: Firdaus
authors.initials: F
authors.lastname: Shahid
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hasan
authors.forename: Nosheen
authors.initials: N
authors.lastname: Nasir
authors.forename: Tashmeem
authors.initials: T
authors.lastname: Razzaki
authors.forename: Ghaffar
authors.initials: G
authors.lastname: Dawood
authors.forename: Rabia
authors.initials: R
authors.lastname: Hussain
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D016207:Cytokines / Q000097:blood*; D019468:Disease Management; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D012720:Severity of Illness Index; D014376:Tuberculosis / Q000097:blood*; D014397:Tuberculosis, Pulmonary / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma