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Elevated serum interleukin-6 associated with a failure in B cell differentiation in common variable immunodeficiency.
- Source :
-
The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 1990 Oct; Vol. 86 (4 Pt 1), pp. 512-21. - Publication Year :
- 1990
-
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.
- Subjects :
- Agammaglobulinemia blood
Agammaglobulinemia genetics
Agammaglobulinemia immunology
B-Lymphocytes immunology
Cell Differentiation immunology
Dysgammaglobulinemia blood
Dysgammaglobulinemia immunology
Genetic Linkage
Humans
Hybridomas immunology
Hypergammaglobulinemia blood
Hypergammaglobulinemia immunology
IgA Deficiency
Immunoglobulin M
Immunologic Deficiency Syndromes immunology
Monocytes immunology
X Chromosome
B-Lymphocytes pathology
Immunologic Deficiency Syndromes blood
Interleukin-6 blood
Subjects
Details
- Language :
- English
- ISSN :
- 0091-6749
- Volume :
- 86
- Issue :
- 4 Pt 1
- Database :
- MEDLINE
- Journal :
- The Journal of allergy and clinical immunology
- Publication Type :
- Academic Journal
- Accession number :
- 2229813
- Full Text :
- https://doi.org/10.1016/s0091-6749(05)80207-6