Profiling and multivariate analysis of serum cytokines in patients with generalized pustular psoriasis

Abstract

Introduction: Generalized pustular psoriasis (GPP) is a chronic autoinflammatory disease characterized by fever, erythema, and sterile pustules occurring over large areas of the skin. The immunopathogenesis of GPP remains poorly understood. We aimed to profile serum cytokine levels in patients with GPP and analyze treatment-associated changes in cytokine levels. Methods: Twenty-four patients who were diagnosed with GPP and received drug treatment, together with 28 unaffected controls, were recruited in this study. Levels of 27 cytokines in serum samples from pre- and post-treated patients as well as unaffected controls were assessed using a Bio-Plex multiplex immunoassay. Multivariate analysis of cytokine levels and clinical parameters was conducted. Results: Serum levels of interleukins interleukin (IL)-1β, IL-1Ra, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, granulocyte colony-stimulating factor (G-CSF), interferon-γ (IFN-γ), IFN-γ-induced protein 10 (IP-10), monocyte chemoattractant protein-1, tumor necrosis factor-α, and vascular endothelial growth factor were significantly elevated (p < .05) in patients with GPP compared with controls. Serum levels of IL-6, G-CSF, IL-8, IFN-γ, IL1-Ra, IL-10, IL-13, and IL-1β were correlated with GPP severity (r > 0.4, p < .001). Following treatment, serum levels of IL-6, IL-7, IL-12, IFN-γ, IL-1β, IL-4, IL-8, IL-10, IL-13, G-CSF, and IP-10 were significantly decreased (p < .05) compared with pretreatment levels. Among these cytokines, levels of IL-6, IL-7, IL-8, IL-12, IL-13, and IP-10 were reduced to normal levels. Conclusion: GPP patients exhibited markedly elevated levels of cytokines and chemokines involved in both type 1 and type 2 immune responses, suggesting hypercytokinemia occurs in GPP patients. IL-6 showed the strongest correlation with GPP disease severity and other clinical parameters such as CRP level and fever, thus representing an index for GPP severity. Our data comprehensively documented the cytokine profiles of GPP patients and may provide insights into GPP pathogenesis.

Exacerbation of generalized pustular psoriasis after administration of granulocyte colony‐stimulating factor in a patient with intravascular large B‐cell lymphoma

“…Furthermore, the study revealed significant associations between serum cytokines, such as G-CSF and IL-8 levels, and disease severity. 4 These results and our clinical case suggest that G-CSF could be an exacerbating factor for GPP.…”

Antiproliferative and Anti-Inflammatory Effects of the Polyphenols Phloretin and Balsacone C in a Coculture of T Cells and Psoriatic Keratinocytes

“…Furthermore, granulocyte colony-stimulating factor (G-CSF) attracts neutrophils and stimulates both their production and activation [ 74 ]. This factor is overexpressed in the serum of patients with generalized pustular psoriasis [ 75 ], a severe type of psoriasis that leads to the formation of multiple pustules on the epidermis, which are populated by neutrophils [ 76 ]. In phloretin-treated cocultures, there was a reduction in G-CSF levels compared with the psoriatic control ( Figure 4 f).…”

Pustular Eruption following COVID-19 Vaccination: A Narrative Case-Based Review

“…Additionally, IL-6, compared with the other cytokines that are raised in pustular psoriasis, showed the strongest correlation with disease severity and systemic inflammation [ 45 ]. IL1 and IL6 are also noted to be high in the blood of patients with AGEP [ 46 , 47 ]. The dysregulated cytokine network triggered by the vaccine can lead to the imbalance of pro-inflammatory cytokines in neutrophilic dermatosis, leading to an overactive neutrophil response and persistent inflammation [ 48 ].…”