Elevated serum interleukin-6 associated with a failure in B cell differentiation in common variable immunodeficiency
D C Adelman1, T Matsuda, T Hirano
1Department of Medicine, University of California, San Francisco School of Medicine 94143-0724.
The Journal of Allergy and Clinical Immunology
|October 1, 1990
Summary
Patients with common variable immunodeficiency (CVI) show high levels of Interleukin-6 (IL-6), a cytokine crucial for B-cell differentiation. This elevated IL-6 is due to hyperproduction, not reduced usage, and doesn't explain the B-cell differentiation defect in CVI.
Area of Science:
- Immunology
- Cytokine Biology
- B-cell Differentiation
Background:
- Interleukin-6 (IL-6) promotes terminal differentiation of B-lymphocytes into immunoglobulin-producing cells.
- Patients with common variable immunodeficiency (CVI) exhibit a defect in B-lymphocyte terminal differentiation.
- The role of IL-6 in CVI pathogenesis requires investigation due to its known effects on B-cells.
Purpose of the Study:
- To investigate the role of Interleukin-6 (IL-6) in the B-cell differentiation defect observed in common variable immunodeficiency (CVI).
- To determine serum IL-6 levels and production by peripheral blood mononuclear cells (PBMC) in CVI patients compared to healthy controls.
Main Methods:
- Serum IL-6 levels were measured using an IL-6-dependent murine hybridoma bioassay in 17 CVI patients and 8 controls.
- Spontaneous and lipopolysaccharide-stimulated IL-6 production by PBMCs were assessed.
- IL-6 bioactivity inhibition was analyzed in patient and control sera.
Main Results:
- 13 out of 17 CVI patients had serum IL-6 levels 2-fold to 18-fold higher than normal controls.
- PBMCs from CVI patients showed significantly higher spontaneous IL-6 production compared to controls.
- Maximal IL-6 production after lipopolysaccharide stimulation was equivalent in both groups, and IL-6 inhibitory substance levels were similar.
Conclusions:
- The B-cell differentiation defect in CVI is not caused by decreased serum IL-6 levels.
- Elevated circulating IL-6 in CVI patients results from hyperproduction, not reduced consumption.
- Persistently high IL-6 levels may contribute to neoplastic and autoimmune complications in CVI.
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