ovalbumin and pomalidomide

Asthma is a chronic inflammatory disease of the airways of the lungs. Pomalidomide (POM) a therapy for multiple myeloma has been stated to have an anti-inflammatory effect. The main goal of the present study was to assess its possible effect on airway contraction and inflammation in a rat model of ovalbumin-induced asthma. Different groups of rats received saline or pomalidomide (0.4, 0.8 mg/kg) or dexamethasone (0.6 mg/kg). The asthma was induced by ovalbumin (OVA). Trachea contraction was assayed by organ bath system. Airway histology was assessed using hematoxylin and eosin method. Serum Tumor necrosis factor alpha (TNF-α) level was analyzed by Enzyme-Linked Immunosorbent Assay and Platelet-derived growth factor (PDGFα) Gene expressions were evaluated by Real-time PCR. Pomalidomide prevented ovalbumin-induced airway contraction and histopathological damage. In addition serum, TNF-α level was significantly (p<0.05) decreased in POM treated animals compared to control (asthmatic animals that received POM vehicle). Results indicate that POM prevented the PDGF expression induced by ovalbumin. In conclusion, we found that pomalidomide ameliorated the symptoms, histopathological changes and inflammatory markers induced by ovalbumin in asthmatic rats and these effects might be related to its anti-inflammatory properties.

Topics: Airway Obstruction; Allergens; Animals; Anti-Inflammatory Agents; Asthma; Disease Models, Animal; Humans; Lung; Male; Ovalbumin; Platelet-Derived Growth Factor; Rats; Rats, Wistar; Thalidomide; Tumor Necrosis Factor-alpha

The IMiDs(®) immunomodulatory compounds lenalidomide and pomalidomide are agents with anti-inflammatory, immunomodulatory and anti-cancer activity. An excellent success rate has been shown for multiple myeloma in phase I/II clinical trials leading to Food and Drug Administration approval of lenalidomide. One mechanism by which these drugs could enhance anti-tumour immunity may be through enhanced dendritic cell (DC) function. Thalidomide, a compound structurally related to lenalidomide and pomalidomide, is known to enhance DC function, and we have investigated whether its analogues, pomalidomide and lenalidomide, also have functional effects on DCs. We used mouse bone marrow-derived DCs treated with 5 or 10 μm pomalidomide, or lenalidomide from day 1 of culture. Treatment with IMiD(®) immunomodulatory compounds increased expression of Class I (H2-Kb), CD86, and pomalidomide also increased Class II (I-Ab) expression in bone marrow-derived DCs, as measured by flow cytometry. Fluorescent bead uptake was increased by up to 45% when DCs were treated with 5 or 10 μm pomalidomide or lenalidomide compared with non-treated DCs. Antigen presentation assays using DCs primed with ovalbumin, and syngeneic T cells from transgenic OTI and OTII mice (containing MHC restricted, ovalbumin-specific, T cells) showed that both pomalidomide and lenalidomide effectively increased CD8(+) T-cell cross-priming (by up to 47%) and that pomalidomide alone was effective in increasing CD4(+) T-cell priming (by 30%). Our observations suggest that pomalidomide and lenalidomide enhance tumour antigen uptake by DCs with an increased efficacy of antigen presentation, indicating a possible use of these drugs in DC vaccine therapies.

Topics: Animals; Antigen Presentation; Antigens, Neoplasm; CD8-Positive T-Lymphocytes; Cells, Cultured; Cross-Priming; Dendritic Cells; Female; Immunologic Factors; Lenalidomide; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Ovalbumin; Thalidomide