Decreased production of interleukin-12 and other Th1-type cytokines in patients with recent-onset systemic lupus erythematosus

Horwitz, David A.; Gray, J. Dixon; Behrendsen, Steven C.; Kubin, Marek; Rengaraju, Manthrasalam; Ohtsuka, Kazuo; Trinchieri, Giorgio

doi:10.1002/1529-0131(199805)41:5<838::aid-art10>3.0.co;2-s

Cited by 193 publications

(73 citation statements)

References 31 publications

(3 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…An assay was developed and used to measure total circulating IFNγ levels. Reported IFNγ levels in the serum are, in general, very low and often undetectable except in certain disease states 35, 36, 37. Following AMG 811 treatment, which prevents IFNγ binding to the receptor, we observed an increase in circulating IFNγ in the serum, as measured in a complex with AMG 811.…”

Section: Discussionmentioning

confidence: 71%

Blockade of Interferon‐γ Normalizes Interferon‐Regulated Gene Expression and Serum CXCL10 Levels in Patients With Systemic Lupus Erythematosus

Welcher

Boedigheimer

Kivitz

et al. 2015

Arthritis & Rheumatology

View full text Add to dashboard Cite

ObjectiveTo assess the safety and immunologic impact of inhibiting interferon‐γ (IFNγ) with AMG 811, a human IgG1 monoclonal antibody against IFNγ, in patients with systemic lupus erythematosus (SLE).MethodsTwenty‐six patients with mild‐to‐moderate, stable SLE were administered placebo or a single dose of AMG 811, ranging from 2 mg to 180 mg subcutaneously or 60 mg intravenously.ResultsSimilar to results previously reported following inhibition of type I IFNs, treatment of SLE patients with AMG 811 led to a dose‐dependent modulation of the expression of genes associated with IFN signaling, as assessed by microarray analysis of the whole blood. The list of impacted genes overlapped with that identified by stimulating human whole blood with IFNγ and with those gene sets reported in the literature to be differentially expressed in SLE patients. Serum levels of IFNγ‐induced chemokines, including IFNγ‐inducible protein 10 (IP‐10), were found to be elevated at baseline in SLE patients as compared to healthy volunteers. In contrast to previously reported results from studies using type I IFN–blocking agents, treatment with AMG 811 led to dose‐related reductions in the serum levels of CXCL10 (IP‐10).ConclusionThe scope and nature of the biomarkers impacted by AMG 811 support targeting of IFNγ as a therapeutic strategy for SLE.

show abstract

Section: Discussionmentioning

confidence: 71%

Blockade of Interferon‐γ Normalizes Interferon‐Regulated Gene Expression and Serum CXCL10 Levels in Patients With Systemic Lupus Erythematosus

Welcher

Boedigheimer

Kivitz

et al. 2015

Arthritis & Rheumatology

View full text Add to dashboard Cite

show abstract

“…This is a critical factor determining the proliferation and differentiation of Th1-related autoreactive cellular immune responses in these disorders [335]. In contrast, systemic lupus erythematosus (SLE) is associated with excessive production of IL-10 and a deficiency in IL-12 and TNF-α production, which skews cytokine production toward a Th2 profile [336,337].…”

Section: Sympathetic Regulation Of Autoimmune Diseasesmentioning

confidence: 99%

Sympathetic modulation of immunity: Relevance to disease

Bellinger

Millar

Perez

et al. 2008

Cellular Immunology

225

185

View full text Add to dashboard Cite

Optimal host defense against pathogens requires cross-talk between the nervous and immune systems. This paper reviews sympathetic-immune interaction, one major communication pathway, and its importance for health and disease. Sympathetic innervation of primary and secondary immune organs is described, as well as evidence for neurotransmission with cells of the immune system as targets. Most research thus far as focused on neural-immune modulation in secondary lymphoid organs, and have revealed complex sympathetic modulation resulting in both potentiation and inhibition of immune functions. SNS-immune interaction may enhance immune readiness during disease-or injury-induced 'fight' responses. Research also indicate that dysregulation of the SNS can significantly affect the progression of immune-mediated diseases. However, a better understanding of neural-immune interactions is needed to develop strategies for treatment of immune-mediated diseases that are designed to return homeostasis and restore normal functioning neural-immune networks.

show abstract

“…In contrast, most investigators have found impairment in IL-12 production in patients with SLE. 90 In lupus mice, an intrinsic defect in the in vitro production of IL-12 by endotoxin-activated macrophages of MRL +/+ and BWF1 mice has been reported. 91 However, other studies in MRL lpr/lpr mice reported on increased IL-12 production by peritoneal macrophages following stimulation with IFN-g and/or lipopolysaccharide (LPS).…”

Section: Cytokinesmentioning

confidence: 99%