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An Anti-IL-12p40 Antibody Down-Regulates Type 1 Cytokines, Chemokines, and IL-12/IL-23 in Psoriasis
- Source :
- The Journal of Immunology. 177:4917-4926
- Publication Year :
- 2006
- Publisher :
- The American Association of Immunologists, 2006.
-
Abstract
- Psoriasis is characterized by activation of T cells with a type 1 cytokine profile. IL-12 and IL-23 produced by APCs are essential for inducing Th1 effector cells. Promising clinical results of administration of an Ab specific for the p40 subunit of IL-12 and IL-23 (anti-IL-12p40) have been reported recently. This study evaluated histological changes and mRNA expression of relevant cytokines and chemokines in psoriatic skin lesions following a single administration of anti-IL-12p40, using immunohistochemistry and real-time RT-PCR. Expression levels of type 1 cytokine (IFN-γ) and chemokines (IL-8, IFN-γ-inducible protein-10, and MCP-1) were significantly reduced at 2 wk posttreatment. The rapid decrease of these expression levels preceded clinical response and histologic changes. Interestingly, the level of an anti-inflammatory cytokine, IL-10, was also significantly reduced. Significant reductions in TNF-α levels and infiltrating T cells were observed in high responders (improvement in clinical score, ≥75% at 16 wk), but not in low responders. Of importance, the levels of APC cytokines, IL-12p40 and IL-23p19, were significantly decreased in both responder populations, with larger decreases in high responders. In addition, baseline levels of TNF-α significantly correlated with the clinical improvement at 16 wk, suggesting that these levels may predict therapeutic responsiveness to anti-IL-12p40. Thus, in a human Th1-mediated disease, blockade of APC cytokines by anti-IL-12p40 down-regulates expression of type 1 cytokines and chemokines that are downstream of IL-12/IL-23, and also IL-12/IL-23 themselves, with a pattern indicative of coordinated deactivation of APCs and Th1 cells.
- Subjects :
- Chemokine
medicine.medical_treatment
Immunology
Antigen-Presenting Cells
Down-Regulation
Interleukin-23
Interferon-gamma
Downregulation and upregulation
Psoriasis
medicine
Interleukin 23
Humans
Immunology and Allergy
RNA, Messenger
Skin
biology
Interleukin-12 Subunit p40
Reverse Transcriptase Polymerase Chain Reaction
business.industry
Interleukins
Antibodies, Monoclonal
Th1 Cells
medicine.disease
Immunohistochemistry
Interleukin-12
Protein Subunits
Cytokine
Interleukin-23 Subunit p19
Interleukin 12
biology.protein
Cytokines
Antibody
business
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 177
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....dc092042f2a0c88ff02ad4c20bff04ce
- Full Text :
- https://doi.org/10.4049/jimmunol.177.7.4917