DECREASED IL-12 PRODUCTION BY POLYMORPHONUCLEAR LEUKOCYTES IN PATIENTS WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS

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, 100 ng/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.