title: Relationship between circulating levels of IFN-gamma, IL-10, CXCL9 and CCL2 in pulmonary and extrapulmonary tuberculosis is dependent on disease severity.
abstract: Protection against Mycobacterium tuberculosis infection is dependent on T cell and macrophage activation regulated by cytokines. Cytokines and chemokines produced at disease sites may be released into circulation. Data available on circulating cytokines in tuberculosis (TB) is mostly on pulmonary TB (PTB) with limited information on extrapulmonary disease (EPul-TB). We measured interferon-gamma (IFN-gamma), interkeukin-10 (IL-10), CXCL9 and CCL2 in sera of patients (n = 80) including; PTB (n = 42), EPul-TB (n = 38) and BCG vaccinated healthy endemic controls (EC, n = 42). EPul-TB patients comprised those with less severe (LNTB) or severe (SevTB) disease. Serum IFN-gamma, IL-10 and CXCL9 levels were significantly greater while CCL2 was reduced in TB patients as compared with EC. IFN-gamma was significantly greater in PTB as compared with LNTB (P = 0.002) and SevTB (P = 0.029). CXCL9 was greater in PTB as compared with LNTB (P = 0.009). In contrast, CCL2 levels were reduced in PTB as compared with LNTB (P = 0.021) and SevTB (P = 0.024). A Spearman's rank correlation analysis determined a positive association between IFN-gamma and IL-10 (rho = 0.473, P = 0.002) and IFN-gamma and CXCL9 (rho = 0.403, P = 0.008) in the PTB group. However, in SevTB, only IFN-gamma and CXCL9 were positively associated (rho = 0.529, P = 0.016). Systemic levels of cytokines are reflective of local responses at disease sites. Therefore, our data suggests that in PTB increased IFN-gamma and CXCL9 balanced by IL-10 may result in a more effective cell mediated response in the host. However, elevated inflammatory chemokines CXCL9 and CCL2 in severe EPul-TB without concomitant down modulatory cytokines may exacerbate disease related pathology and hamper restriction of M. tuberculosis infection.
authors.affiliation: Department of Pathology and Microbiology, The Aga Khan University, Karachi, Pakistan. zahra.hasan@aku.edu
authors.forename: Z
authors.initials: Z
authors.lastname: Hasan
authors.forename: B
authors.initials: B
authors.lastname: Jamil
authors.forename: J
authors.initials: J
authors.lastname: Khan
authors.forename: R
authors.initials: R
authors.lastname: Ali
authors.forename: M A
authors.initials: MA
authors.lastname: Khan
authors.forename: N
authors.initials: N
authors.lastname: Nasir
authors.forename: M S
authors.initials: MS
authors.lastname: Yusuf
authors.forename: S
authors.initials: S
authors.lastname: Jamil
authors.forename: M
authors.initials: M
authors.lastname: Irfan
authors.forename: R
authors.initials: R
authors.lastname: Hussain
mesh_terms: D000328:Adult; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology; D018932:Chemokine CCL2 / Q000097:blood* / Q000276:immunology; D054370:Chemokine CXCL9 / Q000097:blood* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood* / Q000276:immunology; D016753:Interleukin-10 / Q000097:blood* / Q000276:immunology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D018709:Statistics, Nonparametric; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000276:immunology*
chemical_list: D001500:BCG Vaccine; C080810:CXCL9 protein, human; D018932:Chemokine CCL2; D054370:Chemokine CXCL9; C508609:IL10 protein, human; D016753:Interleukin-10; D007371:Interferon-gamma