title: Expression of cytokine mRNA and protein in joints and lymphoid organs during the course of rat antigen-induced arthritis.
abstract: Cytokine expression was assessed during antigen-induced arthritis (AIA) in synovial membrane (SM), inguinal lymph node (LN), and spleen using competitive RT-PCR and sandwich ELISA. In the SM, early elevations of IL-1beta and IL-6 mRNA (by 6 hours; 450- and 200-fold, respectively) correlated with the joint swelling; a 6-fold increase in tumor necrosis factor alpha (TNFalpha) was not significant. Not only IL-2 and IFN-gamma (which increased 10,000-fold and 200-fold, respectively), but also IL-5 and IL-10, increased acutely (6 hours - day 1; 3-fold and 35-fold, respectively) in the SM. In general, the protein levels in the SM for IL-1beta, IL-6, TNFalpha, IFN-gamma, IL-4, and IL-10 (increase from 4-fold to 15-fold) matched the course of mRNA expression. In the inguinal LN, there were early mRNA elevations of IL-6 (a 2.5-fold increase by 6 hours, which correlated positively with the joint swelling) and IL-2 (4-fold by 6 hours), as well as later rises of IL-4 and IL-5 (2.5- and 4-fold, respectively, by day 3). No significant elevations of the corresponding proteins in this tissue were observed, except for IL-1beta (by day 6) and IL-10 (by day 1). In the spleen, there were significant mRNA elevations at 6 hours of IL-1beta (1.5-fold), IL-6 (4-fold; positively correlated with the joint swelling), IFN-gamma (3-fold), and IL-2 (7- to 10-fold). IL-5 and IL-10 (2- and 3-fold, respectively) peaked from 6 hours to day 3 in the spleen. Increases of the corresponding proteins were significant in comparison with day 0 only in the case of IL-2 (day 6). By day 6 (transition to the chronic phase), the mRNA for cytokines declined to or below prearthritis levels in all the tissues studied except for IL-1beta in the SM and IL-6 in the spleen. AIA is thus characterized by four phenomena: early synovial activation of macrophages, T helper (Th)1-like, and Th2-like cells; late, well-segregated Th2-like responses in the inguinal LN; late, overlapping Th1-like/Th2-like peaks in the spleen; and chronic elevation of synovial IL-1beta mRNA and spleen IL-6 mRNA.
authors.affiliation: Experimental Rheumatology Unit, Friedrich Schiller University Jena, Jena, Germany. dirk.pohlers@med.uni-jena.de
authors.forename: Dirk
authors.initials: D
authors.lastname: Pohlers
authors.forename: Angela
authors.initials: A
authors.lastname: Siegling
authors.forename: Eberhard
authors.initials: E
authors.lastname: Buchner
authors.forename: Carsten B
authors.initials: CB
authors.lastname: Schmidt-Weber
authors.forename: Ernesta
authors.initials: E
authors.lastname: Palombo-Kinne
authors.forename: Frank
authors.initials: F
authors.lastname: Emmrich
authors.forename: Rolf
authors.initials: R
authors.lastname: Bräuer
authors.forename: Raimund W
authors.initials: RW
authors.lastname: Kinne
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D007596:Joints / Q000378:metabolism; D008208:Lymphatic System / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D013583:Synovial Membrane / Q000378:metabolism*
chemical_list: D016207:Cytokines; D011506:Proteins; D012333:RNA, Messenger