Statin Modulation of Human T-Cell Proliferation, IL-1 and IL-17 Production, and IFN- T Cell Expression: Synergy with Conventional Immunosuppressive Agents
Open accessAbstract
HMG-CoA reductase inhibitors (statins) have been demonstrated to be immunomodulatory for human immune-mediated disease and in experimental models. The aim of this study was to compare statin-mediated immunosuppressive effects on human T-cell responses in vitro with those of conventional immunosuppressives (dexamethasone, cyclosporin A (CsA), mycophenolate, and rapamycin). Statins (atorvastatin, lovastatin, and simvastatin) were investigated for their modulatory effects on human PBMC viability, cytokine profiles, and T-cell proliferation. At concentrations that inhibited anti-CD3/28-stimulated T-cell proliferation (), simvastatin significantly decreased intracellular CD4+T-cell expression of IFN- () to levels similar to those induced by conventional immunosuppressives. Atorvastatin and lovastatin also decreased IFN- expression, although to a lesser degree (). All three statins reduced levels of IL-17 production (). However, in response to anti-CD3/28 stimulation, simvastatin significantly upregulated IL-1 production (). The profile of cytokines produced in response to anti-CD3/28 stimulation was similar when both atorvastatin and dexamethasone were added as compared with dexamethasone alone, suggesting that atorvastatin can synergise with dexamethasone with respect to immunomodulation of cytokines. This data supports the hypothesis of selective statin-mediated immunomodulatory effects on human immune cells.
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Atorvastatin decreases Th17 responses in various models and in humans.
“Atorvastatin, among other statins, was also shown to decrease Th17 responses in various models and in humans (Aktunc et al., 2011; Li et al., 2011; Jameel et al., 2013; Lappegard et al., 2013).”
From Atorvastatin Reduces the Survival of Candida albicans-Infected BALB/c Mice (2015) · cites this paper as Jameel et al., 2013
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Atorvastatin Reduces the Survival of Candida albicans-Infected BALB/c Mice
Rahal, E. A., Constantin, W. N., Zeidan, N., & Abdelnoor, A. M. (2015) · Frontiers in Microbiology · doi:10.3389/fmicb.2015.01474 · Cited by 14 · see citing works
- Authors
- Jameel, A., Ooi, K. G.-J., Jeffs, N. R., Galatowicz, G., Lightman, S. L., & Calder, V. L.
- Affiliations
- University College London (GB)
- Moorfields Eye Hospital (GB)
- Corresponding author
- Calder, Virginia L.
- ORCID
- Venue
- International Journal of Inflammation
- Publisher
- Wiley
- Published
- 2013
- Volume
- 2013
- Pages
- 1-11
- ISSN
- 2042-0099 (ISSN-L)
- 2090-8040
- PMC
- PMC3789401
- OpenAlex
- W2006205937
- Cited by
- 43
- References
- 53
- Citations by year
- 2026: 1 · 2025: 7 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 1 · 2017: 8 · 2016: 2 · 2015: 4 · 2014: 1
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- International Journal of Inflammation (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- statins, immunomodulation, T cell proliferation, interferon-gamma, IL-17, IL-1β, atorvastatin, lovastatin, simvastatin, dexamethasone, cyclosporine, mycophenolate, rapamycin, CD4+ T cells, cytokine production
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