title: Elevated serum interleukin-6 associated with a failure in B cell differentiation in common variable immunodeficiency.
abstract: Interleukin-6 (IL-6/B cell stimulatory factor 2) has been found to drive activated human B-lymphocytes through the final stages of differentiation to become immunoglobulin-producing cells. Most patients with common variable immunodeficiency (CVI) have B-lymphocytes that fail to differentiate into high-rate immunoglobulin-secreting cells in vivo and in vitro. In view of (1) the known effects of IL-6 to promote B-lymphocyte terminal differentiation and (2) the defect in differentiation in B-lymphocytes of patients with CVI, we believed that it was important to analyze the role of this cytokine in patients with CVI. Using an IL-6-dependent murine hybridoma cell line in a bioassay, serum IL-6 levels were determined in 17 patients with CVI and in eight normal control subjects. Thirteen of the 17 patients with CVI exhibited serum IL-6 levels that were twofold to 18-fold higher than the range (mean, +2 SD) of normal control subjects. Spontaneous IL-6 production by peripheral blood mononuclear cells (PBMC) of patients with CVI was significantly higher than that from normal control subjects, whereas lipopolysaccharide maximally stimulated IL-6 production by PBMCs of patients with CVI or PBMCs of normal control subjects was equivalent. A substance inhibitory of IL-6 bioactivity was found in equivalent amounts in sera of both patients and normal control subjects. Sera from patients with CVI with high IL-6 bioactivity were found to have saturated this IL-6 inhibitory substance, thus resulting in large amounts of free IL-6 in the sera. These studies suggest that the failure of B cells from patients with CVI to terminally differentiate into high-rate immunoglobulin-secreting cells cannot be attributed to a decrease in the serum levels of IL-6 and that the increased circulating IL-6 levels in patients with CVI result from hyperproduction rather than decreased use of IL-6. The persistently elevated levels of IL-6 observed in some patients with CVI may secondarily result in the induction of the neoplastic and autoimmune phenomena associated with this disease.
authors.affiliation: Department of Medicine, University of California, San Francisco School of Medicine 94143-0724.
authors.forename: D C
authors.initials: DC
authors.lastname: Adelman
authors.forename: T
authors.initials: T
authors.lastname: Matsuda
authors.forename: T
authors.initials: T
authors.lastname: Hirano
authors.forename: T
authors.initials: T
authors.lastname: Kishimoto
authors.forename: A
authors.initials: A
authors.lastname: Saxon
mesh_terms: D000361:Agammaglobulinemia / Q000097:blood / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D002454:Cell Differentiation / Q000276:immunology; D004406:Dysgammaglobulinemia / Q000097:blood / Q000276:immunology; D008040:Genetic Linkage; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D006942:Hypergammaglobulinemia / Q000097:blood / Q000276:immunology; D017098:IgA Deficiency; D007075:Immunoglobulin M; D007153:Immunologic Deficiency Syndromes / Q000097:blood* / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood*; D009000:Monocytes / Q000276:immunology; D014960:X Chromosome
chemical_list: D007075:Immunoglobulin M; D015850:Interleukin-6