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Therapeutic effect of the immunomodulatory drug lenalidomide, but not pomalidomide, in experimental models of rheumatoid arthritis and inflammatory bowel disease

2017; Springer Nature; Volume: 49; Issue: 2 Linguagem: Inglês

10.1038/emm.2016.143

2092-6413

Belén López‐Millán, Rafael Díaz de la Guardia, Heleia Roca-Ho, Carmen M. García‐Herrero, Jessie R. Lavoie, Michael Rosu‐Myles, Elena González‐Rey, Francisco O’Valle, Gabriel Criado, Mario Delgado, Pablo Menéndez,

Protein Degradation and Inhibitors

Thalidomide is an immunomodulatory drug (IMiD) with proven therapeutic action in several autoimmune/inflammatory diseases; however, its inherent high toxicity has led to the development of more powerful and safer thalidomide analogs, including lenalidomide and pomalidomide. These are new generation IMiDs that exhibit direct antitumor activity as well as anti-inflammatory/immunomodulatory properties, and are FDA-approved for the treatment of several hematological malignances. Here we investigated the potential therapeutic effects of lenalidomide and pomalidomide in several experimental murine models of autoimmune/inflammatory diseases: 2,4,6-trinitrobenzene sulfonic acid- and dextran sulfate sodium-induced inflammatory bowel disease and type II collagen-induced arthritis. Lenalidomide displayed a strong therapeutic effect in all these models of autoimmune/inflammatory diseases, while the effect of pomalidomide was less pronounced. In vitro experiments confirmed the immunosuppressive effect of both IMiDs on the proliferative response of stimulated human lymphocytes and on the balance of secreted cytokines toward an anti-inflammatory profile. We conclude that lenalidomide may offer a therapeutic opportunity against autoimmune/inflammatory diseases. Trials in mice find the immunomodulatory drug lenalidomide might help treat rheumatoid arthritis (RA) and inflammatory bowel disease (IBS). Lenalidomide is a chemical analog of thalidomide, the drug notorious for causing devastating birth defects when given to pregnant women in the late 1950s and early 1960s. A new generation of safer analogs, however, is showing useful activity in autoimmune and inflammatory conditions, and cancer. Pablo Menendez and colleagues at the University of Barcelona, with co-workers elsewhere in Spain and in Canada, examined the effect of lenalidomide and the related drug pomalidomide in mouse models of RA, an autoimmune disease, and IBS. Lenalidomide displayed a strong therapeutic effect while that of pomalidomide was less pronounced. Further research to reveal the mechanism of action of these drugs could lead to useful new therapies for human disease.