Psoriasis is a common chronic inflammatory disorder of the skin, characterized by hyperproliferation of keratinocytes. Although the etiology of psoriasis has not been fully elucidated, it is thought to be associated with a combination of genetic, immunologic, and environmental factors1. Psoriasis was originally thought to be associated with a T-helper (Th)1/Th2 cytokine imbalance. Measurement of T cell activity after specific antigen challenge and therapeutic inhibition of activated T cells have been performed in a number of studies234, showing that psoriasis is a T cell-mediated disease. Cytokines in the Th1 pathway include interleukin (IL)-2, IL-12, and interferon (IFN)-γ, whereas the Th17 pathway is primarily mediated by IL-23 and IL-17. IL-22 induces hyperplasia and abnormal differentiation of keratinocytes, thereby playing a key role in the pathogenesis of psoriasis156.

Psoriasis is classified into four morphological subtypes (plaque, guttate, pustular, and erythrodermal psoriasis). Plaque-type psoriasis is the most common form (appearing in approximately 90% of patients), and the term ‘psoriasis’ usually refers to this type of psoriasis7. The predominant phenotype, however, may change into other types in the course of disease. For example, chronic plaque psoriasis may transform into inflamed guttate lesions; conversely, guttate psoriasis develops into plaque psoriasis in approximately 70% of patients8. The mechanism underlying this change in psoriatic phenotype is not clearly understood, but it may be related to a hyperactive immune pathology associated with intercurrent infections, differences in susceptibility or disease-modifying genes5. In particular, Christophers5 proposed that a change in cutaneous inflammation from the IL-12 pathway to the IL-23 pathway, and vice versa, affects phenotypes and their stability.

Only a few studies have correlated cytokine levels with psoriasis phenotypes91011. Furthermore, there are a very few studies that have examined gene expression levels of blood inflammatory cytokines in psoriasis cases. Based on the hypothesis that inflammatory cytokine expression varies according to psoriasis phenotypes and that morphological differences indicate distinct potential immunopathogenesis, we measured cytokine mRNA levels in the blood of healthy controls and patients with guttate or plaque psoriasis by real-time reverse transcription polymerase chain reaction (real-time RT-PCR).

Psoriasis is a chronic inflammatory skin disease associated with the induction of Th1 and Th17 cell responses. Although there have been some studies with opposing results, the blood levels of Th1 and Th17 cytokines in patients with psoriasis are reported to be more increased than those of healthy controls91113141516. The findings of the present study show that the gene expression levels of Th1-related and Th17-related cytokines are elevated in patients with psoriasis. We measured blood mRNA levels of six inflammatory cytokines, including Th1-related (IFN-γ, IL-2, and IL-12) and Th17-related (IL-17A, IL-22, and IL-23) cytokines, and analyzed them based on psoriasis phenotypes (guttate or plaque). As expected, the mRNA levels of IL-12p40, IL-17, and IL-22 were elevated in patients with psoriasis compared to those of healthy controls. However, intriguingly, the levels of IL-2, IFN-γ, and IL-23R were lower in the psoriasis group. Therefore, gene expression levels might be influenced by an unknown negative-feedback pathway or there might be a post-transcriptional defect in patients with psoriasis. In the case of IFN-γ, particularly, data on blood cytokine levels in psoriatic patients are controversial617.

Psoriasis manifests in heterogeneous phenotypes, and its morphology may change through the course of the disease. Morphological differences in psoriasis cases are thought to be related to differences in the expression of inflammatory cytokines, particularly Th1-related and Th17-related cytokines. Previous evidence suggests that a change in inflammatory pathways, from IL-12/IFN-γ to IL-23/IL-17 or vice versa, can affect the psoriasis phenotype591418. Christophers5 proposed that activation of predominately Th1-related response results in a the stable plaque morphology, whereas Th17-related activation is associated with guttate or pustular psoriasis types. Our study, which compared the mRNA levels of blood inflammatory cytokines between patients with guttate and plaque psoriasis, revealed no statistically significant differences. A few studies compared blood cytokine levels between psoriasis subgroups; however, their results were contradictory and did not definitively determine whether there is a significant relationship between specific cytokines and phenotypes. Additionally, the results of our study show that the morphological phenotype may not be determined by activities of either the Th1 or Th17 pathway, specifically. Despite this, and even though the difference was not statistically significant, the blood mRNA levels of IFN-γ and IL-23R were higher in the guttate group than in the plaque group. Interestingly, and contrary to our expectations, mRNA levels of IFN-γ, a Th1-related cytokine, were lower in patients with plaque psoriasis than in those with guttate psoriasis. Thus, additional gene expression studies are needed to determine the association between Th1 or Th2 responses and psoriasis phenotype.

In summary, inflammatory cytokine mRNA levels in blood were significantly elevated in patients with psoriasis compared to healthy controls, although specific activities of either the Th1 or the Th17 pathway could not route the morphologic phenotype of psoriasis. A limitation of our study was the small number of patients involved; therefore, these results should be confirmed in future studies with larger sample sizes.