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Updated: Aug 15, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Levamisole causes differential cytokine expression by elicited mouse peritoneal macrophages
E S Kimball1, C R Schneider, M C Fisher
1Oncology and Endocrinology Research, Janssen Research Foundation, Spring House, Pennsylvania 19477.
Insights
Levamisole treatment enhances interleukin-1 (IL-1) production while inhibiting interleukin-6 (IL-6) and tumor necrosis factor (TNF) in macrophages. This cytokine modulation may explain levamisole
Area of Science:
- Immunology
- Pharmacology
Background:
- Macrophages play a crucial role in immune responses and inflammation.
- Cytokines like IL-1, IL-6, and TNF are key mediators of inflammatory processes.
- Levamisole is an immunomodulatory drug with potential therapeutic applications in autoimmune and inflammatory diseases.
Purpose of the Study:
- To investigate the effect of levamisole on the production of IL-1, IL-6, and TNF by macrophages.
- To explore the potential mechanisms by which levamisole modulates cytokine production.
Main Methods:
- Thioglycolate-elicited peritoneal macrophages from C57B1/6J mice were used.
- Mice were administered levamisole orally.
- Macrophages were stimulated with bacterial lipopolysaccharide (LPS) in vitro.
- Cytokine levels (IL-1, IL-6, TNF) were measured.
- Immunoprecipitation and neutralization studies were performed.
Main Results:
- Levamisole administration enhanced IL-1 production twofold.
- IL-6 and TNF production were inhibited by up to 36% and 62%, respectively.
- Similar effects were observed when macrophages were directly stimulated with levamisole in vitro.
- Levamisole appeared to affect cytokine production at the translational level.
- Kinetics studies showed delayed release of IL-6 and TNF.
Conclusions:
- Levamisole differentially modulates macrophage cytokine production, increasing IL-1 while decreasing IL-6 and TNF.
- These findings suggest a mechanism for levamisole's therapeutic effects in inflammatory and autoimmune conditions.
- The modulation of cytokine profiles by levamisole could impact macrophage recruitment and function at sites of injury.
Abstract:
Thioglycolate-elicited peritoneal macrophages from normal C57B1/6J mice were examined in vitro for bacterial lipopolysaccharide (LPS)-stimulated interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF) production. Macrophages from mice administered a single oral dose of levamisole (3 mg/kg) 1 to 4 days prior to macrophage harvest demonstrated a twofold enhancement of IL-1 production compared to vehicle-treated mice. In contrast, IL-6 production and TNF production by the same macrophages were inhibited up to 36 and 62%, respectively, compared to production by macrophages harvested from vehicle-treated mice. Similar results were observed when IL-1 production and TNF production were followed in peritoneal exidate cells directly stimulated with levamisole in vitro. The ex vivo LPS-stimulated IL-1 production was enhanced 4 days after macrophage elicitation, whereas TNF and IL-6 production returned to baseline by 72 h after macrophage recruitment and augmentation. No evidence could be found for the presence of inhibitors of TNF or IL-6. The specificity of the IL-1, IL-6, and TNF bioactivities was demonstrated by neutralization with specific antisera. Immunoprecipitation studies of supernatants from biosynthetically labeled macrophages also revealed augmented IL-1 production and decreased IL-6 and TNF, indicating that levamisole may have affected cytokine production at the translational level. Kinetics studies revealed that ex vivo release of IL-6 and TNF by macrophages from levamisole-dosed mice was delayed compared to production of these cytokines by macrophages harvested from mice given vehicle only. The results may explain, in part, the reported ability of levamisole to ameliorate cases of rheumatoid arthritis or other autoimmune and inflammatory diseases by affecting the relative levels of cytokines produced by macrophages recruited to sites of injury, which are associated with inflammation and acute-phase protein synthesis.
