Granulocyte colony-stimulating-factor-induced psoriasiform dermatitis resembles psoriasis with regard to abnormal cytokine expression and epidermal activation.
Psoriasis is a chronic inflammatory skin disorder characterized by accumulation of Th1-type T cells and neutrophils, regenerative keratinocyte proliferation and differentiation, and enhanced epidermal production of antimicrobial peptides. The underlying cause is unknown, but there are some similarities with the immunologic defense program against bacteria. Development of psoriasiform skin lesions has been reported after administration of granulocyte colony-stimulating factor (G-CSF), a cytokine induced in monocytes by bacterial antigens. To further investigate the relation between this type of cytokine-induced dermatitis and psoriasis, we analyzed the cutaneous cytokine profile [tumor necrosis factor-alpha (TNF-alpha), interferon-gamma, transforming growth factor-beta1 (TGF-beta1), interleukin-10 (IL-10), IL-12p35 and p40, and IL-8] and expression of markers of epidermal activation [Ki-67, cytokeratin-16, major histocompatibility complex (MHC) class II, intercellular adhesion molecule-1 (ICAM-1)] in a patient who developed G-CSF-induced psoriasiform dermatitis by using quantitative real-time reverse transcriptase-polymerase chain reaction and immunohistology. The histologic picture resembled psoriasis with regard to epidermal hyperparakeratosis and the accumulation of lymphocytes in the upper corium. CD8(+) T cells were found to infiltrate the epidermis which was associated with an aberrant expression of Ki-67, cytokeratin-16, MHC class II, and ICAM-1 on adjacent keratinocytes. As compared to normal skin (n = 7), there was an increased expression of TNF-alpha, IL-12p40, and IL-8, a decreased expression of TGF-beta1, and a lack of IL-10, similar to the findings in active psoriasis (n = 8). Therefore, G-CSF may cause a lymphocytic dermatitis that, similar to psoriasis, is characterized by a pro-inflammatory Th1-type cytokine milieu and an epidermal phenotype indicative of aberrant maturation and acquisition of non-professional immune functions.
Mössner
R
R
Department of Dermatology, Georg-August-University Göttingen, Germany.
Beckmann
I
I
Hallermann
C
C
Neumann
C
C
Reich
K
K
D016207:Cytokines / Q000235:genetics*; D003875:Drug Eruptions / Q000276:immunology / Q000503:physiopathology*; D004817:Epidermis / Q000187:drug effects / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D016209:Interleukin-8 / Q000235:genetics; D015603:Keratinocytes / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D021122:Protein Subunits / Q000235:genetics; D011565:Psoriasis / Q000139:chemically induced* / Q000276:immunology / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; C508858:IL12A protein, human; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D016209:Interleukin-8; D021122:Protein Subunits; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor; D018664:Interleukin-12