PMID- 7910873 OWN - NLM STAT- MEDLINE DCOM- 19940627 LR - 20071114 IS - 0023-6837 (Print) IS - 0023-6837 (Linking) VI - 70 IP - 5 DP - 1994 May TI - Cytokine expression, upregulation of intercellular adhesion molecule-1, and leukocyte infiltration in experimental tubulointerstitial nephritis. PG - 631-8 AB - BACKGROUND: Cytokines are intercellular polypeptide messengers that mediate immune and inflammatory responses. The temporal profile of interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha (TNF-alpha), and monocyte chemotactic protein 1 (MCP-1) expression was examined in anti-tubular basement membrane (TBM) antibody-associated tubulointerstitial nephritis (TIN). EXPERIMENTAL DESIGN: TIN was induced by immunization of Brown Norway rats with bovine cortical TBM, whereas control rats received ovalbumin. Whole kidney RNA was assessed with the RNase protection assay 3, 7, 8, 9, 10, 12, and 14 days after immunization. Cytokine mRNA expression was correlated with TNF-alpha bioactivity, renal intercellular adhesion molecule-1 expression, and CD18-positive leukocyte infiltration by immunohistochemistry. RESULTS: Increased IL-1 beta, TNF-alpha, and MCP-1 mRNA relative to glyceraldehyde-3-phosphate dehydrogenase appeared on day 7 when TIN involved 10 to 40% of the cortex, and peaked rapidly on day 8 when there was 60 to 80% cortical involvement (at which time 75 to 80% of the infiltrating cells were neutrophils). The increase in TNF-alpha mRNA correlated with increased bioactivity. The influx of mononuclear cells on day 8 was preceded by the expression of MCP-1 mRNA. The infiltrating leukocytes expressed the leukocyte beta 2-integrin (CD18) and were found in areas with increased intercellular adhesion molecule-1 expression. The mRNAs for IL-1 beta, TNF-alpha, and MCP-1 were undetectable by day 10 (at which time 95% of the infiltrating cells were mononuclear). An increase in IL-1 receptor antagonist mRNA paralleled those of IL-1 beta. The expression of IL-6 mRNA was similar to that for IL-1, except that it disappeared by day 9. CONCLUSIONS: There is a temporal association in the expression of IL-1 beta, TNF alpha, MCP-1, and IL-6 with the upregulation of intercellular adhesion molecule-1 and leukocyte infiltration within the tubulointerstitium in anti-TBM antibody-associated TIN. The narrow window of time through which these cytokines are expressed and the coincidence of their peak expression on day 8 suggest complex cytokine interactions in the pathogenesis of anti-TBM antibody TIN. FAU - Tang, W W AU - Tang WW AD - Department of Immunology, Scripps Research Institute, La Jolla, California. FAU - Feng, L AU - Feng L FAU - Mathison, J C AU - Mathison JC FAU - Wilson, C B AU - Wilson CB LA - eng GR - DK20043/DK/NIDDK NIH HHS/United States GR - DK40251/DK/NIDDK NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Lab Invest JT - Laboratory investigation; a journal of technical methods and pathology JID - 0376617 RN - 0 (Antibodies) RN - 0 (Antisense Elements (Genetics)) RN - 0 (Cell Adhesion Molecules) RN - 0 (Cytokines) RN - 0 (DNA Primers) RN - 0 (Interleukin-1) RN - 0 (RNA Probes) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases) SB - IM MH - Animals MH - Antibodies MH - Antisense Elements (Genetics) MH - Base Sequence MH - Basement Membrane/immunology MH - Cattle MH - Cell Adhesion Molecules/*biosynthesis MH - Cytokines/*biosynthesis MH - DNA Primers MH - *Gene Expression MH - Gene Expression Regulation MH - Glyceraldehyde-3-Phosphate Dehydrogenases/analysis/biosynthesis MH - Immunization MH - Intercellular Adhesion Molecule-1 MH - Interleukin-1/biosynthesis MH - Kidney Cortex/metabolism/pathology MH - Kidney Tubules/*immunology MH - Leukocytes/metabolism/*pathology MH - Molecular Sequence Data MH - Nephritis, Interstitial/immunology/*metabolism/*pathology MH - Polymerase Chain Reaction MH - RNA Probes MH - RNA, Messenger/analysis/*biosynthesis/metabolism MH - Rats MH - Rats, Inbred BN MH - Tumor Necrosis Factor-alpha/biosynthesis EDAT- 1994/05/01 00:00 MHDA- 1994/05/01 00:01 CRDT- 1994/05/01 00:00 PHST- 1994/05/01 00:00 [pubmed] PHST- 1994/05/01 00:01 [medline] PHST- 1994/05/01 00:00 [entrez] PST - ppublish SO - Lab Invest. 1994 May;70(5):631-8.