Effect of selected non-steroidal anti-inflammatory drugs on activation-induced CD25 expression on murine CD4+ and CD8+ T cells: an in vitro study

摘要

The main aim of this study has been to determine the effect of selected non-steroidal anti-inflammatory drugs (NSAIDs) – depending on their selectivity to cyclooxygenase (COX) 1 and 2 – on the activation-induced CD25 expression on CD4⁺ and CD8⁺ T cells. Lymphocytes obtained from lymph nodes of mice were treated with acetylsalicylic acid (ASA; a preferential COX-1 inhibitor), ketoprofen (KET; a non-selective COX inhibitor) and robenacoxib (ROB; a selective COX-2 inhibitor) in concentrations reflecting their plasma levels achieved in vivo at therapeutic doses and in ten-fold lower concentrations. The cells were activated with concanavalin A. In contrast to KET and ROB, ASA had no effect on the activation-induced CD25 expression on CD4⁺ and CD8⁺ T cells, nor did it affect the counts of CD4⁺ and CD8⁺ activated effector (aTeff) and resting (Trest) T cells. Both KET and ROB caused a depletion of CD8⁺ aTeff cells, and additionally KET induced a loss of CD8⁺ Trest cells. Moreover, ROB, but not the other drugs, reduced the activation-induced CD25 expression on CD4⁺ T cells. This suggests that non-selective COX inhibitors and selective COX-2 inhibitors may weaken the effector T cell response by producing a negative effect on the count of aTeff cells. Furthermore, the results seem to imply that ASA and KET have certain potential to induce Foxp3 expression in CD25⁺CD8⁺ and CD25⁺CD4⁺ T cells, respectively. However, all the observed changes were very weakly manifested and therefore it is not certain whether they have clinical importance, despite the statistical significance determined.