title: Ex vivo cytokine mRNA levels correlate with changing clinical status of ethiopian TB patients and their contacts over time.
abstract: There is an increasing body of evidence which suggests that IL-4 plays a role in the pathogenesis of TB, but a general consensus on its role remains elusive. We have previously published data from a cohort of Ethiopian TB patients, their contacts, and community controls suggesting that enhanced IL-4 production is associated with infection with M. tuberculosis, rather than overt disease and that long-term protection in infected community controls is associated with co-production of the IL-4 antagonist IL-4d2, alongside elevated IL-4. Here, for the first time, we compare data on expression of IFN-gamma, IL-4 and IL-4delta2 over time in TB patients and their household contacts. During the follow-up period, the TB patients completed therapy and ceased to display TB-like symptoms. This correlated with a decrease in the relative amount of IL-4 expressed. Over the same period, the clinical status of some of their contacts also changed, with a number developing TB-like symptoms or clinically apparent TB. IL-4 expression was disproportionately increased in this group. The findings support the hypothesis that elevated IL-4 production is generally associated with infection, but that TB disease is associated with a relatively increased expression of IL-4 compared to IFN-gamma and IL-4delta2. However, the data also suggest that there are no clear-cut differences between groups: the immune response over time appears to include changes in the expression of IFN-gamma, IL-4 and IL-4delta2, and it is the relative, not absolute levels of cytokine expression that are characteristic of clinical status.
authors.affiliation: Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
authors.forename: Liya
authors.initials: L
authors.lastname: Wassie
authors.forename: Abebech
authors.initials: A
authors.lastname: Demissie
authors.forename: Abraham
authors.initials: A
authors.lastname: Aseffa
authors.forename: Markos
authors.initials: M
authors.lastname: Abebe
authors.forename: Lawrence
authors.initials: L
authors.lastname: Yamuah
authors.forename: Hiwot
authors.initials: H
authors.lastname: Tilahun
authors.forename: Beyene
authors.initials: B
authors.lastname: Petros
authors.forename: Graham
authors.initials: G
authors.lastname: Rook
authors.forename: Alimuddin
authors.initials: A
authors.lastname: Zumla
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.forename: T Mark
authors.initials: TM
authors.lastname: Doherty
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D016207:Cytokines / Q000235:genetics*; D005002:Ethiopia; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014376:Tuberculosis / Q000097:blood* / Q000473:pathology
chemical_list: D016207:Cytokines; D012333:RNA, Messenger