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Decreased IL-12 production by polymorphonuclear leukocytes in patients with active systemic lupus erythematosus
Chang-Youh Tsai1, Tsai-Hung Wu, Chia-Li Yu
1Section of Allergy, Immunology & Rheumatology, Department of Medicine, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan. cytsai@vghtpe.gov.tw
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)-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.
Insights
Polymorphonuclear leukocytes (PMN) from patients with systemic lupus erythematosus (SLE) show reduced capacity to produce Interleukin-12 (IL-12). This impaired IL-12 production, particularly in the presence of Interferon-gamma (IFN-γ), may contribute to increased infection susceptibility in active SLE.
Area of Science:
- Immunology
- Molecular Biology
- Rheumatology
Background:
- Polymorphonuclear leukocytes (PMN) are crucial for combating bacterial infections.
- Systemic lupus erythematosus (SLE) is associated with an increased risk of infections, suggesting potential immune dysregulation.
Purpose of the Study:
- To investigate the IL-12 production capacity of PMN in patients with active SLE.
- To determine if Interferon-gamma (IFN-γ) affects IL-12 production in SLE PMN.
Main Methods:
- Collected peripheral blood PMN from 25 active SLE patients and 25 healthy controls.
- Stimulated PMN with lipopolysaccharide (LPS) +/- IFN-γ.
- Analyzed IL-12 p35 gene transcription via RT-PCR.
- Quantified IL-12 p70 secretion using EIA.
Main Results:
- PMN from SLE patients exhibited significantly lower IL-12 expression compared to controls at 6 hours post-stimulation.
- Normal PMN produced IL-12 upon LPS stimulation, enhanced by IFN-γ.
- IFN-γ inhibited IL-12 production in SLE PMN stimulated with LPS.
- The IL-12 p35 gene structure was intact in SLE patients' PMN.
Conclusions:
- PMN from active SLE patients demonstrate a defect in IL-12 expression.
- This defect is exacerbated by IFN-γ, which normally enhances IL-12 production.
- Impaired IL-12 response in SLE PMN may contribute to heightened susceptibility to infections.