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. 2025 Apr;97(4):e70320.
doi: 10.1002/jmv.70320.

No Distinct Cytokine, Chemokine, and Growth Factor Blood Profile Associated With Monkeypox Virus Clade IIb Infected Patients

Eugene Bangwen  1   2 , Nicole Berens-Riha  1 , Nicky de Vrij  1   3 , Ann Ceulemans  4 , Isabel Brosius  1 , Elise De Vos  1 , Thao-Thy Pham  1 , Emmanuel Bottieau  1 , Johan van Griensven  1 , Palmer Masumbe Netongo  5   6 , Marjan Van Esbroeck  1 , Koen Vercauteren  1 , Christophe Van Dijck  1 , Wim Adriaensen  1 , Laurens Liesenborghs  1   2
Affiliations

No Distinct Cytokine, Chemokine, and Growth Factor Blood Profile Associated With Monkeypox Virus Clade IIb Infected Patients

Eugene Bangwen et al. J Med Virol. 2025 Apr.

Abstract

Previous studies indicated Clade I monkeypox virus infection to be associated with marked elevation of proinflammatory cytokines. This remains unexplored for Clade II-associated disease, which has different clinical manifestations and prognosis. We used a 65-plex cytokine, chemokine, and growth factor (CCG) panel to analyze serum samples of 100 male acute Clade IIb mpox patients and 26 healthy controls in Belgium. Cluster analyses revealed no strong or distinct CCG profiles distinguishing mpox patients from controls but suggested trends in certain cytokine modulation. Individual CCG analyses found elevated levels of cytokines (MIF, CD30, IL2R, IL18, APRIL, and TNFRII), chemokines (CCL4, CCL8, CCL22, CCL24, CXCL9, CXCL10, CXCL11, CXCL12, and CXCL13), and growth factors (HGF and VEGFA) in patients, while CCL11 and CXCL5 were significantly suppressed. We detected no differences in key proinflammatory cytokines, IL-1α, IL-1β, IL-6, IL-8 or anti-inflammatory cytokines, IL-4, IL-10, IL-13. In patients living with HIV, comparison with pre-outbreak samples showed an increase in CXCL13 and a decrease in CXCL5, CCL2, CCL24, HGF, SCF, and TWEAK. The absence of discriminatory CCG profiles in Clade IIb mpox patients compared to healthy controls suggests there may be limited clinical applications of those markers.

Keywords: cytokines; immunology of mpox; monkeypox virus; mpox.

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Conflict of interest statement

L.L. has received institutional consultancy fees from BioNtech and institutional research funding from Sanofi; both not relevant for this work. All other authors declare no competing interests.

Figures

Figure 1
Figure 1
Heatmap displaying the within‐group median log2‐normalized Z‐scored CCG expression for acutely ill mpox patients versus healthy volunteers.
Figure 2
Figure 2
Z‐scored heatmap of CCG values, as well as clinical characteristics of each participant.
Figure 3
Figure 3
K‐means clustering following PCA on the log2‐normalized and Z‐scored CCG data to confirm the weak clustering observed with the heatmap.
Figure 4
Figure 4
Comparison of the concentration (pg/mL) of individual CCGs in mpox patients (mpox+) and healthy participants (controls). In the case of interaction, we conducted a separate analysis stratified by HIV status. Mpox‐positive participants without HIV (m+H−, n = 80), healthy volunteers (m−H−, n = 26), mpox‐positive participants living with HIV (m+H+, n = 20), and available pre‐outbreak controls for HIV positive participants before mpox (m−H+, n = 10) Associations were tested by Mann–Whitney U test and p values reported. (A) Elevated CCG values in all mpox patients compared to healthy volunteers. (B) Suppressed CCG values in all mpox patients compared to healthy volunteers.
Figure 5
Figure 5
Comparison of the concentration (pg/mL) of individual CCGs in mpox patients with different clinical characteristics. Associations were tested by Mann–Whitney U test and p values reported. (A) Concentrations of individual CCGs in mpox patients with different lesion count categories. (B) Possible association of CXCL11 and CCL24 with the presence of ongoing fever during mpox disease. (C) Evidence of possible association of CD30 with proctitis during mpox disease.
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