title: Role of interleukin-6 in a glucan-induced model of granulomatous vasculitis.
abstract: The role of interleukin-6 (IL-6) in granulomatous vasculitis is not well understood. To investigate its involvement in this type of vasculitis a model of glucan-induced pulmonary vasculitis employed interleukin-6 deficient (IL-6-/-) mice. Briefly, IL-6-/- mice and C57B/J6 wild type (IL-6+/+) mice were injected intravenously with a suspension of glucan isolated from the cell wall of bakers yeast which results in a granulomatous vasculitis primarily in the pulmonary vasculature. Histological examination demonstrated no significant difference in the number of infiltrating leukocytes between the IL-6+/+ and IL-6-/- glucan-injured mice. Similar numbers of granulomas were noted in both the IL-6+/+ and IL-6-/- injured animals, while no granulomas were seen in saline injected control mice. Cells recovered from the bronchoalveolar lavage (BAL) fluid were differentially stained and counted. While there was a significant increase in infiltrating leukocytes recovered from the BAL following glucan-induced injury, there was no significant difference between the IL-6+/+ and IL-6-/- mice. In addition, no difference was demonstrated in total protein content in the BAL fluid between IL-6+/+ and IL-6-/- mice. However, myeloperoxidase (MPO) activity in the lungs of the IL-6-/- mice was less than in their IL-6+/+ counterparts suggesting that these animals have a partial defect in their ability to recruit neutrophils in this model. Studies done to look for levels of other cytokines/chemokines in these animals to compensate for the loss of IL-6 revealed that only IL-10 in the sera (p<0.016) and BAL fluid (p<0.05) of IL-6-/- mice was significantly higher then their IL-6+/+-injured counterparts. These studies suggest that IL-6, while possibly involved in early neutrophil accumulation in this model does not appear critical to the development of the TH-2 mediated granulomatous vasculitis.
authors.affiliation: Department of Pathology, University of Michigan Medical School, 7520 MSRB I, 1301 Catherine Rd., Ann Arbor, MI 48109, USA.
authors.forename: Shannon D
authors.initials: SD
authors.lastname: McClintock
authors.forename: Adam G
authors.initials: AG
authors.lastname: Barron
authors.forename: Eric W
authors.initials: EW
authors.lastname: Olle
authors.forename: Michael P
authors.initials: MP
authors.lastname: Deogracias
authors.forename: Roscoe L
authors.initials: RL
authors.lastname: Warner
authors.forename: Mark R
authors.initials: MR
authors.lastname: Opp
authors.forename: Kent J
authors.initials: KJ
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability; D016207:Cytokines / Q000032:analysis; D005936:Glucans; D015769:Granuloma, Respiratory Tract / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015850:Interleukin-6 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism; D014657:Vasculitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology
chemical_list: D016207:Cytokines; D005936:Glucans; D015850:Interleukin-6; D009195:Peroxidase