title: Interleukin-11 drives early lung inflammation during Mycobacterium tuberculosis infection in genetically susceptible mice.
abstract: IL-11 is multifunctional cytokine whose physiological role in the lungs during pulmonary tuberculosis (TB) is poorly understood. Here, using in vivo administration of specific antibodies against IL-11, we demonstrate for the first time that blocking IL-11 diminishes histopathology and neutrophilic infiltration of the lung tissue in TB-infected genetically susceptible mice. Antibody treatment decreased the pulmonary levels of IL-11 and other key inflammatory cytokines not belonging to the Th1 axis, and down-regulated IL-11 mRNA expression. This suggests the existence of a positive feedback loop at the transcriptional level, which is further supported by up-regulation of IL-11 mRNA expression in the presence of rIL-11 in in vitro cultures of lung cells. These findings imply a pathogenic role for IL-11 during the early phase of Mycobacterium tuberculosis-triggered disease in a genetically susceptible host.
authors.affiliation: Department of Immunology, Central Institute for Tuberculosis, Moscow, Russia.
authors.forename: Marina A
authors.initials: MA
authors.lastname: Kapina
authors.forename: Galina S
authors.initials: GS
authors.lastname: Shepelkova
authors.forename: Vadim G
authors.initials: VG
authors.lastname: Avdeenko
authors.forename: Anna N
authors.initials: AN
authors.lastname: Guseva
authors.forename: Tatiana K
authors.initials: TK
authors.lastname: Kondratieva
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Evstifeev
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Apt
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000627:therapeutic use; D019898:Autocrine Communication; D005260:Female; D020022:Genetic Predisposition to Disease; D017370:Interleukin-11 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011014:Pneumonia / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology*; D014158:Transcription, Genetic; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology*
chemical_list: D000906:Antibodies; D017370:Interleukin-11