Serum cytokine concentrations correlate with the severity of imiquimod and IL-23-induced psoriatic inflammation in mice

Izabela Krzemień; Angelika Szatan; Paulina Skalska; Martyna Cieślik; Angelika Domagała; Magdalena Gębicka; Krzysztof Bryniarski; Katarzyna Nazimek; Izabela Krzemień; Angelika Szatan; Paulina Skalska; Martyna Cieślik; Angelika Domagała; Magdalena Gębicka; Krzysztof Bryniarski; Katarzyna Nazimek

doi:10.3934/Allergy.2024016

AIMS Allergy and Immunology

2024, Volume 8, Issue 4: 265-282. doi: 10.3934/Allergy.2024016

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Research article

Serum cytokine concentrations correlate with the severity of imiquimod and IL-23-induced psoriatic inflammation in mice

Department of Immunology, Jagiellonian University Medical College, 18 Czysta St., 31-121 Krakow, Poland

Received: 11 October 2024 Revised: 08 November 2024 Accepted: 20 November 2024 Published: 25 November 2024

Plaque psoriasis is dominated by a T helper cell-mediated autoimmune response, while interleukin (IL)-36 and neutrophil-induced autoinflammation underlies generalized pustular psoriasis; these pathomechanisms are characterized by similar dysregulation of cytokine circuits. Thus, monitoring serum cytokine concentrations seems to have a great diagnostic value. However, the exact relationship between serum cytokine levels and disease severity in psoriatic patients is not established, and no data are available on this relationship in mouse models of psoriasis. Therefore, we aimed to analyze the correlation between serum cytokine concentrations and severity of psoriatic inflammation induced in female C57BL/6 mice with either imiquimod (IMQ) or IL-23. To better reflect the heterogeneity of the systemic course of psoriasis, we diversified the study mouse population by jointly analyzing both models at two different time points and by calculating the cumulative score that simultaneously described the modified psoriasis area severity index (mPASI), ear swelling response, and splenomegaly index for each mouse separately. Compared to intradermally injected IL-23, topically administered IMQ causes significantly more severe psoriatic inflammation characterized by higher serum cytokine levels, mPASI scores, and ear swelling response together with spleen enlargement. Accordingly, serum concentrations of tumor necrosis factor alpha (TNFα) and p40 subunit of IL-12 and IL-23 positively correlated with disease severity, while IL-6 showed a negative correlation. Moreover, the mPASI value was not the only predictor of serum levels of these cytokines, which highlights the importance of assessing other clinical and laboratory parameters in psoriasis monitoring. This approach would enable a comprehensive analysis of systemic autoinflammatory and autoimmune reactions in psoriasis, determine the risk of complications and comorbidities, and select targeted therapy.
- autoimmunity,
- autoinflammation,
- cytokines,
- disease severity,
- imiquimod,
- IL-23,
- mouse models of psoriasis,
- PASI,
- pro-inflammatory cytokines,
- rodent models of psoriasis
Citation: Izabela Krzemień, Angelika Szatan, Paulina Skalska, Martyna Cieślik, Angelika Domagała, Magdalena Gębicka, Krzysztof Bryniarski, Katarzyna Nazimek. Serum cytokine concentrations correlate with the severity of imiquimod and IL-23-induced psoriatic inflammation in mice[J]. AIMS Allergy and Immunology, 2024, 8(4): 265-282. doi: 10.3934/Allergy.2024016

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Abstract

Plaque psoriasis is dominated by a T helper cell-mediated autoimmune response, while interleukin (IL)-36 and neutrophil-induced autoinflammation underlies generalized pustular psoriasis; these pathomechanisms are characterized by similar dysregulation of cytokine circuits. Thus, monitoring serum cytokine concentrations seems to have a great diagnostic value. However, the exact relationship between serum cytokine levels and disease severity in psoriatic patients is not established, and no data are available on this relationship in mouse models of psoriasis. Therefore, we aimed to analyze the correlation between serum cytokine concentrations and severity of psoriatic inflammation induced in female C57BL/6 mice with either imiquimod (IMQ) or IL-23. To better reflect the heterogeneity of the systemic course of psoriasis, we diversified the study mouse population by jointly analyzing both models at two different time points and by calculating the cumulative score that simultaneously described the modified psoriasis area severity index (mPASI), ear swelling response, and splenomegaly index for each mouse separately. Compared to intradermally injected IL-23, topically administered IMQ causes significantly more severe psoriatic inflammation characterized by higher serum cytokine levels, mPASI scores, and ear swelling response together with spleen enlargement. Accordingly, serum concentrations of tumor necrosis factor alpha (TNFα) and p40 subunit of IL-12 and IL-23 positively correlated with disease severity, while IL-6 showed a negative correlation. Moreover, the mPASI value was not the only predictor of serum levels of these cytokines, which highlights the importance of assessing other clinical and laboratory parameters in psoriasis monitoring. This approach would enable a comprehensive analysis of systemic autoinflammatory and autoimmune reactions in psoriasis, determine the risk of complications and comorbidities, and select targeted therapy.

Acknowledgments

We would like to thank Mr. Maciej Panek, MSc, and Mrs. Jolanta Wątor for housing and taking care of the laboratory animals. This work was supported by Polish Ministry of Science and Higher Education under awards number N41/DBS/001026 and N41/DBS/001285 to KN.

Conflict of interest

The authors declare no conflict of interest.

Author contributions

IK performed the experiments, analyzed the data and drafted the manuscript. AS performed the experiments and analyzed the data. PS performed the experiments and ELISA tests. MC, AD and MG participated in the experiments. KB conceived and supervised the study and revised the manuscript. KN conceived and designed the study, performed the experiments, analyzed the data, drafted the manuscript and received funding. All authors have read and approved the final manuscript.

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