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

**Authors:** Eugene Bangwen, Nicole Berens‐Riha, Nicky de Vrij, Ann Ceulemans, Isabel Brosius, Elise De Vos, Thao‐Thy Pham, Emmanuel Bottieau, Johan van Griensven, Palmer Masumbe Netongo, Marjan Van Esbroeck, Koen Vercauteren, Christophe Van Dijck, Wim Adriaensen, Laurens Liesenborghs

PMC · DOI: 10.1002/jmv.70320 · Journal of Medical Virology · 2025-03-29

## TL;DR

The study found no distinct blood cytokine profiles in monkeypox patients infected with Clade IIb, suggesting limited clinical use of these markers.

## Contribution

The study is the first to analyze cytokine profiles in Clade IIb monkeypox patients using a 65-plex panel.

## Key findings

- No strong cytokine profiles distinguished Clade IIb mpox patients from healthy controls.
- Some cytokines, chemokines, and growth factors were elevated or suppressed in patients.
- HIV-positive patients showed changes in specific cytokine levels compared to pre-outbreak samples.

## 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.

## Linked entities

- **Proteins:** MIF (macrophage migration inhibitory factor), TNFRSF8 (TNF receptor superfamily member 8), IL2RA (interleukin 2 receptor subunit alpha), IL18 (interleukin 18), TNFSF13 (TNF superfamily member 13), TNFRSF1B (TNF receptor superfamily member 1B), CCL4 (C-C motif chemokine ligand 4), CCL8 (C-C motif chemokine ligand 8), CCL22 (C-C motif chemokine ligand 22), CCL24 (C-C motif chemokine ligand 24), CXCL9 (C-X-C motif chemokine ligand 9), CXCL10 (C-X-C motif chemokine ligand 10), CXCL11 (C-X-C motif chemokine ligand 11), CXCL12 (C-X-C motif chemokine ligand 12), CXCL13 (C-X-C motif chemokine ligand 13), HGF (hepatocyte growth factor), VEGFA (vascular endothelial growth factor A), CCL11 (C-C motif chemokine ligand 11), CXCL5 (C-X-C motif chemokine ligand 5), IL1A (interleukin 1 alpha), IL1B (interleukin 1 beta), IL6 (interleukin 6), CXCL8 (C-X-C motif chemokine ligand 8), IL4 (interleukin 4), IL10 (interleukin 10), IL13 (interleukin 13), CCL2 (C-C motif chemokine ligand 2), KITLG (KIT ligand), TNFSF12 (TNF superfamily member 12)
- **Diseases:** monkeypox (MONDO:0002594)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, KITLG (KIT ligand) [NCBI Gene 4254] {aka DCUA, DFNA69, FPH2, FPHH, KL-1, Kitl}, TNFRSF8 (TNF receptor superfamily member 8) [NCBI Gene 943] {aka CD30, D1S166E, Ki-1}, IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559] {aka CD25, IDDM10, IL2R, IMD41, TCGFR, p55}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, CCL24 (C-C motif chemokine ligand 24) [NCBI Gene 6369] {aka Ckb-6, MPIF-2, MPIF2, SCYA24}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, CCL8 (C-C motif chemokine ligand 8) [NCBI Gene 6355] {aka HC14, MCP-2, MCP2, SCYA10, SCYA8}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, HGF (hepatocyte growth factor) [NCBI Gene 3082] {aka DFNB39, F-TCF, HGFB, HPTA, SF}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, CXCL13 (C-X-C motif chemokine ligand 13) [NCBI Gene 10563] {aka ANGIE, ANGIE2, BCA-1, BCA1, BLC, BLR1L}, CXCL11 (C-X-C motif chemokine ligand 11) [NCBI Gene 6373] {aka H174, I-TAC, IP-9, IP9, SCYB11, SCYB9B}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, CCL4 (C-C motif chemokine ligand 4) [NCBI Gene 6351] {aka ACT2, AT744.1, G-26, HC21, LAG-1, LAG1}, CXCL12 (C-X-C motif chemokine ligand 12) [NCBI Gene 6387] {aka IRH, PBSF, SCYB12, SDF1, TLSF, TPAR1}, CXCL9 (C-X-C motif chemokine ligand 9) [NCBI Gene 4283] {aka CMK, Humig, MIG, SCYB9, crg-10}, MIF (macrophage migration inhibitory factor) [NCBI Gene 4282] {aka GIF, GLIF, MMIF}, CXCL5 (C-X-C motif chemokine ligand 5) [NCBI Gene 6374] {aka ENA-78, SCYB5}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, TNFSF12 (TNF superfamily member 12) [NCBI Gene 8742] {aka APO3L, DR3LG, TNF12, TNLG4A, TWEAK}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, CCL22 (C-C motif chemokine ligand 22) [NCBI Gene 6367] {aka A-152E5.1, ABCD-1, DC/B-CK, MDC, SCYA22, STCP-1}, CCL11 (C-C motif chemokine ligand 11) [NCBI Gene 6356] {aka SCYA11}, TNFRSF1B (TNF receptor superfamily member 1B) [NCBI Gene 7133] {aka CD120b, TBPII, TNF-R-II, TNF-R75, TNFBR, TNFR1B}
- **Diseases:** Clade I monkeypox virus infection (MESH:D045908), Clade II-associated disease (MESH:D004194), inflammatory (MESH:D007249)
- **Species:** Monkeypox virus (no rank) [taxon 10244], Human immunodeficiency virus 1 (no rank) [taxon 11676], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11954153/full.md

## References

25 references — full list in the complete paper: https://tomesphere.com/paper/PMC11954153/full.md

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Source: https://tomesphere.com/paper/PMC11954153