title: Constitutive production of proinflammatory cytokines RANTES, MIP-1beta and IL-18 characterizes LGL leukemia.
abstract: Large granular lymphocyte (LGL) leukemia is a lymphoproliferative disease often associated with autoimmune disorders such as rheumatoid arthritis. High levels of soluble Fas ligand have been implicated in development of chronic neutropenia. However, a comprehensive analysis of constitutive chemokine and lymphokine production in LGL leukemia has not previously been reported. Here, we utilized RNase protection assays and enzyme-linked immunosorbent assays (ELISAs) to address this question. RANTES, IL-8, MIP-1alpha, MIP-1beta, IL-1beta, IL-10, IL-12 p35, IL-18, IFN-gamma and IL-1Ra were the cytokine transcripts expressed in elevated levels from RNA of peripheral blood mononuclear cells of LGL leukemia patients. Confirmatory ELISAs indicated that sera from LGL leukemia patients have elevated levels of RANTES, MIP-1beta, IL-18, and to a lesser extent IL-8 and IL-1Ra. This pattern of cytokine upregulation is similar to that seen in some chronic infections or in autoimmune diseases, thus characterizing LGL leukemia as a proinflammatory disorder.
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. kothapar@moffitt.usf.edu
authors.forename: Ravi
authors.initials: R
authors.lastname: Kothapalli
authors.forename: Susan B
authors.initials: SB
authors.lastname: Nyland
authors.forename: Irina
authors.initials: I
authors.lastname: Kusmartseva
authors.forename: Ratna D
authors.initials: RD
authors.lastname: Bailey
authors.forename: Tylee M
authors.initials: TM
authors.lastname: McKeown
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Loughran
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid; D001327:Autoimmune Diseases / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation; D053590:Interleukin 1 Receptor Antagonist Protein; D020382:Interleukin-18 / Q000096:biosynthesis*; D007945:Leukemia, Lymphoid / Q000097:blood* / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008875:Middle Aged; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D020382:Interleukin-18; D019402:Macrophage Inflammatory Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D012313:RNA