title: Differential effects of ageing on cytokine and chemokine responses during type-1 (mycobacterial) and type-2 (schistosomal) pulmonary granulomatous inflammation in mice.
abstract: Cytokine and chemokine responses during anamnestic type-1 and type-2 lung granuloma formation were evaluated in mice at 6,12,18 and 24-months of age. Lesions were induced by embolizing Sepharose beads coupled to Mycobacterium bovis purified protein derivative or soluble Schistosoma mansoni egg antigens. Type-1 inflammation was reduced by 18 months, whereas type-2 granulomas not until 24 months of age. In type-1 draining lymph nodes cultures, interferon-gamma (IFNgamma) declined to a nadir by 18, and then partly recovered at 24 months. In contrast, IL-4 was not significantly impaired in type-2 cultures until 24 months. Type-1 and 2 node cultures also displayed decreased IL-13, but paradoxically enhanced IL-5 production at 24 months. Chemokine transcripts in granulomatous lungs displayed age-related alterations. In the type-1 response, CXCL9 (monokine-induced by IFNgamma) declined with age then partly recovered at 24 months parallelling lymph node IFNgamma levels. Transcripts for MIP-2/CXCL2, IP-10/CXCL10, MCP-1/CCL2, and MCP-5/CCL12 increased at 24 months. In the type-2 response MCP-1/CCL2, MCP-3/CCL7, MCP-5/CCL12 and TARC/CCL17 collapsed at 24 months paralleling local IL-4 transcript levels, yet some chemokine transcripts such as KC/CXCL1 and eotaxin/CCL11 were unaffected. These findings suggest that cytokine and chemokine responses degrade differentially with age shifting Th1/Th2 crossregulatory pressures and local expression of chemokines.
authors.affiliation: Department of Pathology, University of Michigan Medical School, 113 Ann Arbor Veterans Affairs Healthcare System, 2215 Fuller Road, Ann Arbor, MI 48105, USA.
authors.forename: Bo Chin
authors.initials: BC
authors.lastname: Chiu
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Shang
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Frait
authors.forename: Jerry S
authors.initials: JS
authors.lastname: Hu
authors.forename: Eric
authors.initials: E
authors.lastname: Komuniecki
authors.forename: Richard A
authors.initials: RA
authors.lastname: Miller
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Chensue
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis*; D015769:Granuloma, Respiratory Tract / Q000276:immunology* / Q000473:pathology; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000473:pathology; D014376:Tuberculosis / Q000276:immunology* / Q000473:pathology
chemical_list: D018925:Chemokines; D016207:Cytokines