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Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice

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Abstract.

Objective and Design:

To investigate whether ivermectin, a semi-synthetic derivative of a family of macrocyclic lactones could inhibit lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro.

Materials and Methods:

C57BL/6 mice were administered ivermectin (or saline) orally and challenged intraperitoneally with LPS at a lethal dose of 32 mg/kg. RAW 264.7 murine macrophages were stimulated with LPS at 1 μg/ml, with or without ivermectin for 6, 12 and 24 h. The production of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in serum from mice and supernatants from cells were measured by ELISA. Nuclear factor-kB (NF-kB) translocation with subunit p65 was evaluated by immunocytochemical analysis.

Results:

Ivermectin improved mouse survival rate induced by a lethal dose of LPS. In addition, ivermectin significantly decreased the production of TNF-α, IL-1ß and IL-6 in vivo and in vitro. Furthermore, ivermectin suppressed NF-kB translocation induced by LPS.

Conclusions:

The results indicate that ivermectin may inhibit LPS-induced production of inflammatory cytokines by blocking NF-kB pathway and improve LPS-induced survival in mice. This finding might provide a new strategy for the treatment of endotoxemia and associated inflammation.

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Correspondence to J. Cui or X. Deng.

Additional information

Xuemei Zhang and Yu Song contributed equally to this work

Received 13 January 2008; returned for revision 7 February 2008; received from final revision 3 April 2008; accepted by M. Parnham 4 April 2008

Xuemei Zhang and Yu Song contributed equally to this work

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Zhang, X., Song, Y., Ci, X. et al. Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice. Inflamm. res. 57, 524–529 (2008). https://doi.org/10.1007/s00011-008-8007-8

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  • DOI: https://doi.org/10.1007/s00011-008-8007-8

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