Ivermectin enhances the transcription of pro-inflammatory cytokines in equine leukocytes stimulated with LPS and nigericin.
- 1Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, 5090000, Chile.
Abstract
Ivermectin has been reported to exert immunomodulatory effects on the innate immune system; however, the available evidence is contradictory, with both anti-inflammatory and, paradoxically, pro-inflammatory effects described depending on species, dose, and experimental context, while data specific to horses remain scarce. We hypothesised that ivermectin would exert a context-dependent immunomodulatory effect on equine leucocytes. To test this, total leucocytes isolated from six healthy horses were incubated with ivermectin (2 and 4 µg/mL) before stimulation with lipopolysaccharide (LPS) and nigericin. Gene expression of the pro-inflammatory cytokines IL-1β, IL-6, IL-8, TNF-α, and IL-18, together with key components of the NLRP3 inflammasome (NLRP3, ASC/PYCARD, and CASP-1), was quantified by RT-qPCR, and leucocyte viability was assessed using the MTT assay. Ivermectin significantly increased transcript levels of IL-1β, IL-6, and IL-8 following LPS and nigericin stimulation, without affecting leucocyte viability at concentrations up to 12 µg/mL. In contrast, the gene expression of NLRP3, ASC/PYCARD, and CASP-1 was not significantly altered. As the study assessed only mRNA levels, without markers of functional inflammasome activation, this finding is reported as secondary and exploratory rather than as evidence that the canonical inflammasome pathway is uninvolved. Overall, these results provide novel evidence of a pro-inflammatory transcriptional effect of ivermectin in equine leucocytes, a species markedly underrepresented in this field, and underscore the need for further studies using pharmacokinetically relevant concentrations and protein-level or functional assessments to clarify the underlying mechanisms and the clinical relevance of these effects in equine inflammatory conditions.
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BibTeX
@article{apaoblaza2026ivermectin,
title = {{Ivermectin enhances the transcription of pro-inflammatory cytokines in equine leukocytes stimulated with LPS and nigericin.}},
author = {Sofia Apaoblaza and Alejandro Albornoz and Claudio Henriquez and John Quiroga and Rafael A Burgos and Gabriel Moran},
journal = {Veterinary and animal science},
year = {2026},
month = oct,
doi = {10.1016/j.vas.2026.100894},
url = {https://europepmc.org/article/MED/42927118},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Ivermectin enhances the transcription of pro-inflammatory cytokines in equine leukocytes stimulated with LPS and nigericin.
AU - Sofia Apaoblaza
AU - Alejandro Albornoz
AU - Claudio Henriquez
AU - John Quiroga
AU - Rafael A Burgos
AU - Gabriel Moran
PY - 2026
DA - 2026/10/09
JO - Veterinary and animal science
DO - 10.1016/j.vas.2026.100894
UR - https://europepmc.org/article/MED/42927118
AB - Ivermectin has been reported to exert immunomodulatory effects on the innate immune system; however, the available evidence is contradictory, with both anti-inflammatory and, paradoxically, pro-inflammatory effects described depending on species, dose, and experimental context, while data specific to horses remain scarce. We hypothesised that ivermectin would exert a context-dependent immunomodulatory effect on equine leucocytes. To test this, total leucocytes isolated from six healthy horses were incubated with ivermectin (2 and 4 µg/mL) before stimulation with lipopolysaccharide (LPS) and nigericin. Gene expression of the pro-inflammatory cytokines IL-1β, IL-6, IL-8, TNF-α, and IL-18, together with key components of the NLRP3 inflammasome (NLRP3, ASC/PYCARD, and CASP-1), was quantified by RT-qPCR, and leucocyte viability was assessed using the MTT assay. Ivermectin significantly increased transcript levels of IL-1β, IL-6, and IL-8 following LPS and nigericin stimulation, without affecting leucocyte viability at concentrations up to 12 µg/mL. In contrast, the gene expression of NLRP3, ASC/PYCARD, and CASP-1 was not significantly altered. As the study assessed only mRNA levels, without markers of functional inflammasome activation, this finding is reported as secondary and exploratory rather than as evidence that the canonical inflammasome pathway is uninvolved. Overall, these results provide novel evidence of a pro-inflammatory transcriptional effect of ivermectin in equine leucocytes, a species markedly underrepresented in this field, and underscore the need for further studies using pharmacokinetically relevant concentrations and protein-level or functional assessments to clarify the underlying mechanisms and the clinical relevance of these effects in equine inflammatory conditions.
SN - 2451-943X
ER -