title: Mycobacterial glycolipid cord factor trehalose 6,6'-dimycolate causes a decrease in serum cortisol during the granulomatous response.
abstract: Serum cortisol levels were evaluated in mice following intravenous administration of purified mycobacterial glycolipid trehalose 6,6'-dimycolate (TDM). C57BL/6 mice develop lung granulomas in response to TDM, while A/J mice are deficient in this process. Administration of TDM to C57BL/6 mice led to a rapid reduction in serum cortisol, concurrent with initiation of the granulomatous response and cytokine and chemokine mRNA induction. Cortisol levels were lowest on day 5 after TDM administration, but there was significant production of IL-6, TNF-alpha and IL-1beta messages. Granuloma formation and full immune responsiveness to TDM were only apparent upon a sufficient decrease in levels of systemic cortisol. Treatment of the C57BL/6 mice with hydrocortisone abolished inflammatory responses. Histologically nonresponding A/J mice exhibited higher constitutive serum cortisol and demonstrated different kinetics of cortisol reduction upon administration of TDM. A/J mice demonstrated hyperplastic morphology in the suprarenal gland with a high degree of vacuolization in the medullary region and activation of cells in the zona fasciculata and zona reticularis. The A/J mice were dysregulated with respect to cytokine responses thought to be necessary during granuloma formation. The high constitutive serum cortisol in the A/J mice may therefore contribute to pulmonary immunoresponsiveness and the establishment of an environment counterproductive to the initiation of granulomatous responses. The identification of a mycobacterial glycolipid able to influence serum cortisol levels is unique and is discussed in relation to immunopathology during tuberculosis disease.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, TX 77030, USA. Jeffrey.K.Actor@uth.tmc.edu
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Actor
authors.forename: Jessica
authors.initials: J
authors.lastname: Indrigo
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Beachdel
authors.forename: Margaret
authors.initials: M
authors.lastname: Olsen
authors.forename: Alice
authors.initials: A
authors.lastname: Wells
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hunter
authors.forename: Amitava
authors.initials: A
authors.lastname: Dasgupta
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology / Q000502:physiology; D000313:Adrenal Medulla / Q000166:cytology / Q000502:physiology; D000818:Animals; D003311:Cord Factors / Q000276:immunology / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D015769:Granuloma, Respiratory Tract / Q000097:blood* / Q000139:chemically induced / Q000276:immunology*; D006854:Hydrocortisone / Q000097:blood*; D007155:Immunologic Factors / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000276:immunology*
chemical_list: D003311:Cord Factors; D016207:Cytokines; D007155:Immunologic Factors; D006854:Hydrocortisone