title: Cytokine gene activation in synovial membrane, regional lymph nodes, and spleen during the course of rat adjuvant arthritis.
abstract: Cytokine gene activation was assessed during rat adjuvant arthritis (AA) in synovial membrane (SM), popliteal lymph node (popl-LN), and spleen, using semiquantitative, competitive RT-PCR. Changes in the popl-LN were considerably higher than in spleen or SM. In the preclinical phase (day 6), cytokine mRNA elevations occurred exclusively in the popl-LN and included IFN-gamma, IL-1beta, IL-5, IL-6, and IL-10. In the acute phase (days 13-16) all three organs became involved: (i) in the SM, significant elevations were limited to IL-1beta and IL-6, which, notably, correlated positively with the degree of arthritis; (ii) in the popl-LN, IFN-gamma, IL-1beta, IL-6, and IL-10 (but not IL-5) were still elevated, while IL-2 rose significantly; (iii) in the spleen, TNF-alpha peaked simultaneously with the arthritis score (day 16) and dramatically dropped thereafter. Upon transition into the chronic phase (day 20) the following phenomena were observed: (i) IL-1beta and IL-6 were still significantly increased in the SM; (ii) IFN-gamma, IL-1beta, IL-2, IL-6, and IL-10 were still elevated in the popl-LN; and (iii) there was a progressive rise of IL-5 mRNA in the spleen, positively correlated with the arthritis score. In conclusion, cytokines with pro- and anti-inflammatory functions overlap throughout disease, but in different organ-related patterns. Local (SM) and regional (popl-LN) IL-1beta and IL-6, elevated throughout the entire course of AA, may directly contribute to disease severity. While in AA spleen TNF-alpha appears to be a systemic marker of acute disease, spleen IL-5 may be involved in disease resolution.
authors.affiliation: Swiss Institute for Asthma and Allergy Research (SIAF), Davos, CH-7270, Switzerland.
authors.forename: C B
authors.initials: CB
authors.lastname: Schmidt-Weber
authors.forename: D
authors.initials: D
authors.lastname: Pohlers
authors.forename: A
authors.initials: A
authors.lastname: Siegling
authors.forename: H
authors.initials: H
authors.lastname: Schädlich
authors.forename: E
authors.initials: E
authors.lastname: Buchner
authors.forename: H D
authors.initials: HD
authors.lastname: Volk
authors.forename: E
authors.initials: E
authors.lastname: Palombo-Kinne
authors.forename: F
authors.initials: F
authors.lastname: Emmrich
authors.forename: R W
authors.initials: RW
authors.lastname: Kinne
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000503:physiopathology; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006968:Hypersensitivity, Delayed / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D012333:RNA, Messenger; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology; D015533:Transcriptional Activation
chemical_list: D016207:Cytokines; D012333:RNA, Messenger