Therapeutic effect of the immunomodulatory drug lenalidomide, but not pomalidomide, in experimental models of rheumatoid arthritis and inflammatory bowel disease.
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.
Department of Biomedicine, School of Medicine, Josep Carreras Leukemia Research Institute, University of Barcelona, Barcelona, Spain.
Belen
B
Lopez-Millan
Department of Biomedicine, School of Medicine, Josep Carreras Leukemia Research Institute, University of Barcelona, Barcelona, Spain.
Rafael
R
Diaz de la Guardia
Department of Biomedicine, School of Medicine, Josep Carreras Leukemia Research Institute, University of Barcelona, Barcelona, Spain.
Heleia
H
Roca-Ho
Inflammatory and Autoimmune Diseases Group, Hospital 12 de Octubre Research Institute, Madrid, Spain.
Carmen M
CM
García-Herrero
Centre for Biologics Evaluation, Biologics and Genetic Therapies Directorate, Health Products and Food Branch, Health Canada, Ontario, Ottawa, Canada.
Jessie R
JR
Lavoie
Centre for Biologics Evaluation, Biologics and Genetic Therapies Directorate, Health Products and Food Branch, Health Canada, Ontario, Ottawa, Canada.
Michael
M
Rosu-Myles
Instituto de Parasitología y Biomedicina 'López Neyra', Armilla, Granada, Spain.
Elena
E
Gonzalez-Rey
Department of Pathology, School of Medicine, University of Granada, Granada, Spain.
Francisco
F
O'Valle
Inflammatory and Autoimmune Diseases Group, Hospital 12 de Octubre Research Institute, Madrid, Spain.
Gabriel
G
Criado
Instituto de Parasitología y Biomedicina 'López Neyra', Armilla, Granada, Spain.
Mario
M
Delgado
Department of Biomedicine, School of Medicine, Josep Carreras Leukemia Research Institute, University of Barcelona, Barcelona, Spain.|Instituciò Catalana Recerca i Estudis Avançats (ICREA), Pg Lluís Companys 23, Barcelona, Spain.
Pablo
P
Menendez
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D024043:Collagen Type II; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D007155:Immunologic Factors / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000077269:Lenalidomide; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014302:Trinitrobenzenesulfonic Acid
D000893:Anti-Inflammatory Agents; D024043:Collagen Type II; D007155:Immunologic Factors; D013792:Thalidomide; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate; C467566:pomalidomide; D000077269:Lenalidomide