Decreased IL-12 production by polymorphonuclear leukocytes in patients with active systemic lupus erythematosus
Journal
Immunological Investigations
Journal Volume
31
Journal Issue
3月4日
Pages
177-189
Date Issued
2002
Author(s)
Abstract
Polymorphonuclear leukocytes (PMN) play an important role in eradicating bacterial infections. To test if PMN of patients with systemic lupus erythematosus (SLE) have defective capacity to produce IL-12, IL-12 p35 gene transcription and p70 excretion by PMN were evaluated in SLE patients and normal subjects. Peripheral blood PMN from 25 patients with active SLE and 25 normal individuals were stimulated with lipopolysaccharide (LPS, 100ng/mL) in the presence or absence of recombinant interferon (IFN)-γ (5-200 IU/mL). The IL-12 p35 gene transcripts were analyzed by reverse transcription - polymerase chain reaction (RT-PCR) and the IL-12 p70 in culture supernatants was quantified by enzyme immunoassay (EIA). At the 6th hour of stimulation, IL-12 expression in PMN of SLE patients was less prominent than that of the normal controls. The IL-12 was produced by normal PMN on LPS stimulation in the absence of IFN-γ. IFN-γ enhanced the IL-12 production by normal PMN stimulated with LPS, but it inhibited the IL-12 production in PMN from active lupus patients in the presence of LPS. Analysis with PCR using the same primers on the chromosomal DNA showed that p35 gene was intact in SLE patients. These results have suggested that SLE-PMN may have defect in IL-12 expression and the defect may be exaggerated in the presence of IFN-γ which normally stimulates IL-12 production. This may account for increased susceptibility to multiple infections in patients with active SLE.
Subjects
IL-12; Interferon γ; Polymorphonuclear neutrophils; Systemic lupus erythematosus
SDGs
Other Subjects
DNA; gamma interferon; interleukin 12; lipopolysaccharide; protein p35; IL12A protein, human; interleukin 12; interleukin 12p35; interleukin 12p40; lipopolysaccharide; protein subunit; recombinant gamma interferon; article; clinical article; controlled study; cytokine production; enzyme immunoassay; human; immunopathogenesis; immunoregulation; interferon production; neutrophil; priority journal; reverse transcription polymerase chain reaction; systemic lupus erythematosus; transcription regulation; adolescent; adult; autoimmune disease; biosynthesis; blood; cell culture; comparative study; drug effect; female; gene expression regulation; genetics; hospitalization; male; metabolism; middle aged; systemic lupus erythematosus; Adolescent; Adult; Autoimmune Diseases; Cells, Cultured; Female; Gene Expression Regulation; Humans; Interferon-gamma, Recombinant; Interleukin-12; Interleukin-12 Subunit p35; Interleukin-12 Subunit p40; Lipopolysaccharides; Lupus Erythematosus, Systemic; Male; Middle Aged; Neutrophils; Protein Subunits; Reverse Transcriptase Polymerase Chain Reaction; Severity of Illness Index
Publisher
Marcel Dekker Inc.
Type
journal article