title: IP-10 detection in urine is associated with lung diseases.
abstract: BACKGROUND
  Blood cytokines and chemokines have been proposed as biomarkers for tuberculosis (TB). Recently, some immune mediators found in the urine of patients with renal dysfunctions have also been suggested as potential biomarkers. Finding biomarkers for TB in urine would present several advantages over blood in terms of collection and safety. The objective of this study was to investigate the presence of cytokines and chemokines in the urine of patients with pulmonary TB at the time of diagnosis. In a subgroup, the evaluation was also performed during TB treatment and at therapy completion. Patients with lung diseases other than TB, and healthy subjects were also enrolled.
  
  
  METHODS
  Urine samples from 138 individuals, after exclusion of renal dysfunctions, were collected during an 18 month-period. Among them, 58 received a diagnosis of pulmonary TB, 28 resulted having lung diseases other than TB, and 34 were healthy subjects. Moreover, 18 TB patients, 9 of whom were tested 2 months after AFB smear sputum reversion and 9 of whom were cured of TB were also included. Cytokines and chemokines in urine were evaluated using a Cytometric-Bead-Array-Flex-Set. IP-10 detection in 49 subjects was also carried out in parallel by using an Enzyme Linked ImmunoSorbent Assay (ELISA).
  
  
  RESULTS
  IFN-γ, TNF-α, IL-2, IL-8, MIP-1α, MIP-1β and RANTES were poorly detected in all urine samples. Conversely, IP-10 was consistently detected in urine and its level was significantly increased in patients with lung disease compared to healthy subjects (p < 0.001). Increased IP-10 levels were found in both pulmonary TB and lung diseases other than TB. Moreover lower IP-10 levels were found in cured-TB patients compared to the levels at the time of diagnosis, and this difference was close to significance (p = 0.06). Interestingly, we demonstrated a significant correlation between the data obtained by flow cytometry and ELISA (r² 0.82, p < 0.0001).
  
  
  CONCLUSIONS
  IP-10, in contrast to IFN-γ, TNF-α, IL-2, IL-8, MIP-1α, MIP-1β and RANTES, is detectable in the urine of patients with pulmonary diseases in the absence of renal dysfunctions. Moreover, the IP-10 level in cured-TB patients is comparable to that found in healthy subjects. More studies are needed to further investigate the clinical utility of these findings.
authors.affiliation: Department of Epidemiology and Preclinical Research, L. Spallanzani National Institute for Infectious Diseases (INMI), Rome, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Cannas
authors.forename: Ludovica
authors.initials: L
authors.lastname: Calvo
authors.forename: Teresa
authors.initials: T
authors.lastname: Chiacchio
authors.forename: Gilda
authors.initials: G
authors.lastname: Cuzzi
authors.forename: Valentina
authors.initials: V
authors.lastname: Vanini
authors.forename: Francesco N
authors.initials: FN
authors.lastname: Lauria
authors.forename: Luigia
authors.initials: L
authors.lastname: Pucci
authors.forename: Enrico
authors.initials: E
authors.lastname: Girardi
authors.forename: Delia
authors.initials: D
authors.lastname: Goletti
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000652:urine; D054357:Chemokine CXCL10 / Q000652:urine*; D018925:Chemokines / Q000652:urine; D016207:Cytokines / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008171:Lung Diseases / Q000652:urine*; D008297:Male; D014397:Tuberculosis, Pulmonary / Q000628:therapy / Q000652:urine*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D018925:Chemokines; D016207:Cytokines