Interferon-alpha regulation of lymphocyte function in systemic lupus erythematosus.
Interferon (IFN) production and responsiveness are abnormal in some patients with systemic lupus erythematosus (SLE). The present investigation was designed to further delineate these abnormalities of IFN response. The response to IFN-alpha was determined in peripheral blood mononuclear cells (PBMC) using the natural killer (NK) cell assay, the concanavalin A (Con A)-induced T-cell proliferation assay, and the pokeweed mitogen (PWM) blastogensis system. The average NK cell activity was impaired in SLE patients (19.7 +/- 3.8 LU/10(7) cells; n = 22) compared to 24 normal controls (45.6 +/- 7.2 LU/10(7) cells; n = 24) (P less than 0.05). In addition, the response to IFN in the NK cell system was impaired in SLE (110.0 +/- 38.0% enhancement) compared to controls (320.0 +/- 94.0% enhancement; +/- SD P less than 0.05). In contrast to the impaired IFN response of the NK cell in SLE, the effect of IFN on Con A- and PWM-induced blastogenesis in SLE was normal (P greater than 0.1). Thus, the defect in IFN response in SLE appeared to be confined to the NK cell system, but was not present in the other assay systems. To determine if the impaired IFN response might be secondary to impaired release of natural killer cytotoxic factor (NKCF) induced by IFN, NKCF was generated from PBMC in the presence of IFN. IFN-induced NKCF release was markedly impaired in SLE (8.9 +/- 11.7%) relative to normal controls (22.3 +/- 11.2%) (P less than 0.05). IFN-induced release of NKCF in SLE also closely correlated with IFN-induced NK enhancement (r = .83, P less than 0.05). No depletion of NK cells was noted using the monoclonal antibody HNK-1. Thus, this study demonstrates for the first time that the insensitivity to IFN in SLE is not a universal lymphocyte defect but appears to be isolated to the NK cell which is functionally abnormal.
D000328:Adult; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis
D007370:Interferon Type I