Aberrant Inflammation in Psoriatic Disease
Psoriatic disease is associated with aberrant inflammation and the production of proinflammatory mediators. Current research regarding the immunopathogenesis of psoriasis supports the theory of a dysregulated immune system governed by proinflammatory cytokines, including TNF-α, IL-17, IL-23, and other cytokines.11, 12, 13 Increased levels of proinflammatory mediators are found in lesions and synovium of patients with psoriatic disease.40, 41More about aberrant inflammation in psoriatic disease »
Psoriasis and psoriatic arthritis are inflammatory diseases with shared immunologic mechanisms.2 Once an immune cell has been activated, it releases proinflammatory mediators that can then activate other cells and promote proliferation, recruiting more cells to the site of disease. In psoriatic disease, this process does not resolve but disrupts immune homeostasis, thus creating a chronic cycle of inflammation.2
Abnormal levels of pro- and anti-inflammatory mediators in joint-resident cells in the synovium could explain the characteristic swelling and tenderness of psoriatic arthritis.40, 41 Research into the role of the various pro- and anti-inflammatory mediators in synovial fluid of patients with psoriatic arthritis is ongoing.
When inflammatory dysregulation activates keratinocytes in the skin, the keratinocytes proliferate and the skin becomes inflamed; the result is the creation of psoriatic plaques.31 PDE4 is an intracellular enzyme that promotes production of proinflammatory mediators and decreases production of anti-inflammatory mediators.3, 4, 5, 6
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See PDE4’s Role in Autoimmune Disease
The general term for histologically apparent cytologic changes, cellular infiltration, and mediator release that occurs in affected blood vessels and adjacent tissue in response to injury or abnormal stimulation. The so‑called cardinal signs of rubor (redness), calor (heat), tumor (swelling), and dolor (pain) may or may not be present.
Any of a group of multifunctional cytokines synthesized by lymphocytes, monocytes, macrophages, and lymphoid and nonlymphoid cells.
A key enzyme involved in the cytokine production of inflammatory cells. PDE4 is an intracellular enzyme that promotes inflammation by degrading intracellular levels of cyclic adenosine monophosphate (cAMP), a naturally occurring second messenger that helps maintain immune homeostasis by modulating the production of pro‑ and anti‑inflammatory mediators.
A common dermatologic condition characterized by the eruption of circumscribed, discrete and confluent, reddish, silvery‑scaled maculopapules; the lesions occur predominantly on the elbows, knees, scalp, and trunk, and microscopically show characteristic parakeratosis and elongation of rete ridges with shortening of epidermal keratinocyte transit time due to decreased cyclic guanosine monophosphate
A form of polyarthritis (ie, affecting more than one joint) that occurs in patients with psoriasis; the arthritis resembles rheumatoid arthritis but is seronegative for rheumatoid factor and often involves the digits.
Any of several cytokines that function as cell‑associated or secreted proteins interacting with receptors of the tumor necrosis factor receptor (TNFR) family.
- 2 Joshi R. Immunopathogenesis of psoriasis. Indian J Dermatol Venereol Leprol. 2004;70:10‑12.
- 3 Souness JE, Griffin M, Maslen C, et al. Evidence that cyclic AMP phosphodiesterase inhibitors suppress TNF alpha generation from human monocytes by interacting with a 'low‑affinity' phosphodiesterase 4 conformer. Br J Pharmacol. 1996;118:649‑658.
- 4 Ma R, Yang BY, Wu CY. A selective phosphodiesterase 4 (PDE4) inhibitor Zl‑n‑91 suppresses IL‑17 production by human memory Th17 cells. Int Immunopharmacol. 2008;8:1408‑1417.
- 5 Essayan DM, Huang SK, Kagey‑Sobotka A, Lichtenstein LM. Effects of nonselective and isozyme selective cyclic nucleotide phosphodiesterase inhibitors on antigen‑induced cytokine gene expression in peripheral blood mononuclear cells. Am J Respir Cell Mol Biol. 1995;13:692‑702.
- 6 Oger S, Mehats C, Dallot E, Cabrol D, Leroy MJ. Evidence for a role of phosphodiesterase 4 in lipopolysaccharide‑stimulated prostaglandin E2 production and matrix metalloproteinase‑9 activity in human amniochorionic membranes. J Immunol. 2005;174:8082‑8089.
- 11 Jimenez JL, Punzon C, Navarro J, Munoz‑Fernandez MA, Fresno M. Phosphodiesterase 4 inhibitors prevent cytokine secretion by T lymphocytes by inhibiting nuclear factor‑kappaB and nuclear factor of activated T cells activation. J Pharmacol Exp Ther. 2001;299:753‑759.
- 12 Liu J, Chen M, Wang X. Calcitonin gene‑related peptide inhibits lipopolysaccharide‑induced interleukin‑12 release from mouse peritoneal macrophages, mediated by the cAMP pathway. Immunology. 2000;101:61‑67.
- 13 Sheibanie AF, Tadmori I, Jing H, Vassiliou E, Ganea D. Prostaglandin E2 induces IL‑23 production in bone marrow‑derived dendritic cells. FASEB J. 2004;18:1318‑1320.
- 31 Johnson‑Huang LM, McNutt NS, Krueger JG, Lowes MA. Cytokine‑producing dendritic cells in the pathogenesis of inflammatory skin diseases. J Clin Immunol. 2009;29:247‑256.
- 40 Boniface K, Guignouard E, Pedretti N, et al. A role for T cell‑derived interleukin 22 in psoriatic skin inflammation. Clin Exp Immunol. 2007;150:407‑415.
- 41 van Kuijk AW, Reinders‑Blankert P, Smeets TJ, Dijkmans BA, Tak PP. Detailed analysis of the cell infiltrate and the expression of mediators of synovial inflammation and joint destruction in the synovium of patients with psoriatic arthritis: implications for treatment. Ann Rheum Dis. 2006;65:1551‑1557.