Rupatadine treatment is associated to atherosclerosis worsening and altered T lymphocytes

Background and Aims. Rupatadine is a second-generation anti-histamine and a PAF antagonist, currently employed for the treatment of allergies. It displays anti-inflammatory properties through the inhibition of macrophages and granulocytes recruitment. The anti-inflammator y and antiplatelet ef fects showed by r upatadine could be exploited against atherosclerosis development. Methods. Apolipoprotein E-deficient female mice (n=15 per group) were fed Western-type diet, with (Rupatadine) or without (Control) 0,017% w/w rupatadine for 12 weeks. Results. Weight gain, food and water intake and organ weights were similar in both groups. Also, plasma cholesterol and triglyceride levels were comparable. Atherosclerotic plaque extent in the aorta was comparable between groups. Unexpectedly, rupatadine treatment worsened plaque development in the aortic sinus, without altering necrotic core area, extracellular matrix and neutral lipids deposits and the presence of macrophages. The treatment increased the levels of T lymphocytes intraplaque (+70%) and around the aor tic sinus (+80%). Rupatadine ef fects on T cells were also evaluated with in vitro tests, which showed that rupatadine did not affect cell proliferation, but promoted the polarization of CD4+ towards Th1 and Th2 subsets. No difference in inflammatory infiltrates was detected in liver, lung, kidney, lymph node and spleen. Conclusion. In conclusion, rupatadine treatment in EKO mice fed Western diet resulted in a moderate worsening of atherosclerosis development and an altered T lymphocyte activation.