Normal mitogen-induced suppression of the interleukin-6 (IL-6) response and its deficiency in systemic lupus erythematosus.
A low-frequency suppressor-cell population in normal peripheral blood inhibits the B-cell CESS response to IL-6, following pokeweed mitogen stimulation. The suppression of IL-6 responsiveness is (i) radiation sensitive, (ii) directed against CESS targets and not mediated by inhibition of IL-6 production, and (iii) associated with nonspecific cytotoxic activity against CESS targets. The generation of these cytolytic cells is also radiation sensitive. A correlation was found between PWM-induced cytotoxicity against CESS and the suppression of IL-6-dependent IgG production. But cytotoxicity toward CESS targets is not responsible for this suppression because (i) IL-2 induces equivalent or greater nonspecific cytotoxicity against CESS in the total absence of suppression of CESS-derived IgG production and (ii) suppression is also induced by mitogen-activated PBL separated from CESS targets by a cell-impermeable membrane. This suppression was not mediated by TNF alpha/beta or IFN-gamma. In systemic lupus erythematosus, suppression of IL-6-dependent IgG production is impaired in patients with active disease (29.2 +/- 13.7%) compared to patients with inactive disease (70 +/- 19.5%) or normal controls (82.8 +/- 9.2%). There is also a defect in mitogen-induced nonspecific cytotoxicity in active SLE (specific lysis 15.1 +/- 3.5%, compared to 34 +/- 4% in normals). Pokeweed mitogen-activated PBL can therefore normally induce suppression of B-cell IL-6 responses and this response is deficient in lupus.
Warrington
R J
RJ
Department of Medicine, University of Manitoba, Winnipeg, Canada.
Rutherford
W J
WJ
D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000528:radiation effects; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008297:Male; D011043:Pokeweed Mitogens / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D007074:Immunoglobulin G; D015850:Interleukin-6; D011043:Pokeweed Mitogens; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma