The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
The Pro-Inflammatory Cytokine, Interleukin-6, Enhances the Polarization of Alternatively Activated Macrophages
Open accessAbstract
Macrophages are important innate immune cells that are associated with two distinct phenotypes: a pro-inflammatory (or classically activated) subset with prototypic macrophage functions such as inflammatory cytokine production and bactericidal activity, and an anti-inflammatory (or alternatively activated (AAM)) subset linked with wound healing and tissue repair processes. In this study, we examined the effect of interlukein-6 on human and murine macrophage polarization. The results indicate that despite being commonly associated with pro-inflammatory functions and being implicated in the pathogenesis/pathophysiology of numerous inflammatory diseases, interleukin-6 can enhance the polarization of AAMs, based on increased expression of hallmark markers: arginase-1, Ym1 and CD206; this effect required the AAM differentiating cytokines, IL-4 and IL-13. Co-treatment of AAMs with IL-6 resulted in spontaneous release of IL-10, suppressed LPS-induced nitric oxide production and inhibited cytokine production by activated CD4+ T cells - immunoregulatory features not observed in the 'parent' IL-4+IL-13-induced AAM. The effect of IL-6 required signal transducer and activator of transcription (STAT)-3, was partially dependent on up-regulation of the IL4Rα chain, and was independent of autocrine IL-10. In the presence of IFNγ, IL-6 promoted the production of IL-1β and TNFα suggesting that this cytokine can enhance the phenotype to which a macrophage has committed. This finding may explain the pleiotrophic nature of IL-6, where it is associated with the perpetuation and enhancement of disease in inflammatory situations, but is also necessary for resolution of inflammation and adequate wound healing to occur in others. Thus, the potential benefit of IL-6 in promoting an AAM, with its' anti-inflammatory and wound healing ability, may need to be considered in immunotherapies aimed at in vivo modulation or inhibition of IL-6.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Analyzing real-time PCR data by the comparative CT method
Schmittgen, T. D., & Livak, K. J. (2008) · Nature Protocols · doi:10.1038/nprot.2008.73 · Cited by 26,190
Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144
The chemokine system in diverse forms of macrophage activation and polarization
MANTOVANI, A., SICA, A., SOZZANI, S., ALLAVENA, P., VECCHI, A., & LOCATI, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.09.015 · Cited by 6,534
Alternative activation of macrophages
Gordon, S. (2003) · Nature Reviews Immunology · doi:10.1038/nri978 · Cited by 6,189
Alternative activation of macrophages: mechanism and functions
Gordon, S., & Martinez, F. O. (2010) · Immunity · doi:10.1016/j.immuni.2010.05.007 · Cited by 4,197
Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm
Biswas, S. K., & Mantovani, A. (2010) · Nature Immunology · doi:10.1038/ni.1937 · Cited by 3,840
Nitric oxide and the immune response
Bogdan, C. (2001) · Nature Immunology · doi:10.1038/ni1001-907 · Cited by 3,447
IL‐6: Regulator of Treg/Th17 balance
Kimura, A., & Kishimoto, T. (2010) · European Journal of Immunology · doi:10.1002/eji.201040391 · Cited by 1,595
Xing, Z., Gauldie, J., Cox, G., Baumann, H., Jordana, M., Lei, X. F., & Achong, M. K. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1368 · Cited by 1,498
Steinman, L. (2007) · Nature Medicine · doi:10.1038/nm1551 · Cited by 1,376
Cited by
Wang, D., Wang, X., Si, M., Yang, J., Sun, S., Wu, H., Cui, S., Qu, X., & Yu, X. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.01.005 · Cited by 322
Interleukin 6 as an Energy Allocator in Muscle Tissue
Kistner, T. M., Pedersen, B. K., & Lieberman, D. E. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00538-4 · Cited by 295
Gonzalez-Gil, A. M., & Elizondo-Montemayor, L. (2020) · Nutrients · doi:10.3390/nu12061899 · Cited by 278
“IL-6◦ Ob and T2DM: ↑ [69]+ AE: ↑ (Healthy [70]+) CE: ↓ (basal levels) (Healthy and Ob [70]+) ↑ (via MAPK/JNK/AP-1): OCN [71], oxidative stress [70]+ ↓: glucose intake during exercise [70]+ ↑: IL-10, IL-1Ra, cortisol [72], GLP-1 [73] (indirectly ↑insulin), and OCN [71] ↓: TNF-α [9]+ and IL-1β [74] AT/Immune: ↑lipolysis…”
Macrophages: A review of their role in wound healing and their therapeutic use
Snyder, R. J., Lantis, J., Kirsner, R. S., Shah, V., Molyneaux, M., & Carter, M. J. (2016) · Wound Repair and Regeneration · doi:10.1111/wrr.12444 · Cited by 245
Hu, L., Yu, Y., Huang, H., Fan, H., Hu, L., Yin, C., Li, K., Fulton, D. J. R., & Chen, F. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00696 · Cited by 100
“For in vitro activation of IL-6 trans-signaling experiment, 16HBE and 3T3 were treated with recombinant IL-6 10 ng/ml (R&D Systems, Minneapolis, MN, USA) for 48 h (46).”
Method
Metadata
- Authors
- Fernando, M. R., Reyes, J. L., Iannuzzi, J., Leung, G., & McKay, D. M.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-04-15
- Volume
- 9
- Issue
- 4
- Pages
- e94188
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W1993264795
- Cited by
- 314
- References
- 37
- FWCI
- 9.21
- Type
- journal article
- Language
- en
- Open access
- gold
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: The Pro-Inflammatory Cytokine, Interleukin-6, Enhances the Polarization of Alternatively Activated Macrophages. https://app.cochat.ai/papers/10.1371/journal.pone.0094188
- The paper
- Fernando, M. R., Reyes, J. L., Iannuzzi, J., Leung, G., & McKay, D. M. (2014). The Pro-Inflammatory Cytokine, Interleukin-6, Enhances the Polarization of Alternatively Activated Macrophages. PLoS ONE. https://doi.org/10.1371/journal.pone.0094188
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
