Decreased IL-12 production by polymorphonuclear leukocytes in patients with active systemic lupus erythematosus.
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)-gamma (5-200IU/mL). The IL-12 p35 gene transcripts were analyzed by reverse transcription - polymerase chain reaction (RT-PCR) and the IL-12 p70 in culture supenatants 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-gamma. IFN-gamma 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-gamma which normally stimulates IL-12 production. This may account for increased susceptibility to multiple infections in patients with active SLE.
Tsai
Chang-Youh
CY
Section of Allergy, Immunology & Rheumatology, Department of Medicine, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan. cytsai@vghtpe.gov.tw
Wu
Tsai-Hung
TH
Yu
Chia-Li
CL
Tsai
Ying-Yang
YY
Chou
Chung-Tei
CT
D000293:Adolescent; D000328:Adult; D001327:Autoimmune Diseases / Q000097:blood* / Q000235:genetics; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D008070:Lipopolysaccharides / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D021122:Protein Subunits / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index
C508858:IL12A protein, human; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D008070:Lipopolysaccharides; D021122:Protein Subunits; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma