Defective phagocytosis, decreased tumour necrosis factor-alpha production, and lymphocyte hyporesponsiveness predispose patients with systemic lupus erythematosus to infections.
Twenty-three patients with systemic lupus erythematosus (SLE) were studied in order to understand the mechanism of increased susceptibility to infection in SLE patients. We found that phagocytosis by polymorphonuclear leucocytes (PMN) was significantly defective in untreated (24.2 +/- 3.1%) and immunosuppressant-treated SLE patients (30.0 +/- 3.6%) compared with normals (47.9 +/- 0.6%), while the generation of superoxide anion radicals was normal. The defective phagocytosis in SLE could be increased by human recombinant tumour necrosis factor alpha (TNF-alpha). However, the percentages of phagocytosis in SLE before and after TNF-alpha stimulation were 56.6% and 60.7% of the normal values. This indicates that certain populations of PMN in SLE are not only defective as regards phagocytosis but also unresponsive to TNF-alpha stimulation. In an ELISA, TNF-alpha production by phorbol myristate acetate (PMA)-stimulated mononuclear cells from SLE patients was significantly decreased (181.4 +/- 22.7 pg/ml vs. 533.0 +/- 81.9 pg/ml, p = 0.002). In addition, the percentage of phytohaemagglutinin (PHA)-stimulated mononuclear cells in S phase in the cell cycle was deficient in patients with SLE (17.2 +/- 1.8% vs. 29.7 +/- 2.9%, p less than 0.001). These results lead us to propose that defective PMN in spontaneous and TNF-alpha-induced phagocytosis, decreased production of TNF-alpha, and lymphocyte hyporesponsiveness predispose patients with SLE to infections.
Yu
C L
CL
Department of Medicine, Taiwan Veterans General Hospital, Taipei, ROC.
Chang
K L
KL
Chiu
C C
CC
Chiang
B N
BN
Han
S H
SH
Wang
S R
SR
D000293:Adolescent; D000328:Adult; D002453:Cell Cycle; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis; D011994:Recombinant Proteins / Q000276:immunology; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides