title: In vitro studies on the influence of dexamethasone and meloxicam on bovine WC1+ γδ T cells.
abstract: In view of the lack of data on the effect of meloxicam (non-steroidal anti-inflammatory drug) on bovine γδ T cells (WC1(+) cells) and very poorly recognized effects of dexamethasone (steroidal anti-inflammatory drug) on these cells, the purpose of the present study has been to determine the in vitro influence of these drugs on CD25(high)WC1(+), CD25(low)WC1(+) and CD25(-)WC1(+) lymphocytes of the peripheral blood of cattle. Peripheral blood mononuclear cells were treated with the drugs in concentrations reflecting their plasma levels achieved in vivo at therapeutic doses (dexamethasone 10(-7)M; meloxicam 5×10(-6)M) and at ten-fold lower concentrations. It was found out that percentages and absolute counts of CD25(high)WC1(+) and CD25(low)WC1(+) cells increased in the presence of dexamethasone, and this effect was at least partly attributable to lower mortality of these cells, whose apoptosis was depressed by exposure to dexamethasone. It seems certain that this effect was not a result of increased multiplication of CD25(high)WC1(+) and CD25(low)WC1(+) cells because their proliferation was reduced in the presence of dexamethasone. Exposure to this drug caused a rapidly occurring and lasting depletion of CD25(-)WC1(+), which was at least partly due to their higher apoptosis. The results seem to suggest that impaired proliferation of these cells was responsible for a more profound expression of this disorder. Paradoxically, the percentage of cells producing IFN-γ, a proinflammatory cytokine, increased in the presence of dexamethasone, whereas the count of cells secreting the key anti-inflammatory and immunosuppressive cytokine, i.e. IL-10, declined. This effect was observed in all analyzed subpopulations of cells. Meloxicam did not interfere so drastically as dexamethasone with the functioning of WC1(+) lymphocytes because it did not affect their apoptosis, proliferation, percentage or absolute count. With respect to the effect of meloxicam on counts of particular WC1(+) lymphocyte subpopulations, it was only demonstrated that exposure to the drug was correlated with a transient and very weakly expressed decrease in the relative and absolute counts of CD25(high)WC1(+) and CD25(low)WC1(+) cells, which was most probably a result of a temporary down-regulation of the expression of the CD25 molecule. In the presence of meloxicam, percentages of IFN-γ(+)CD25(-)WC1(+) cells as well as cells producing IL-10 declined, an effect observed in all analyzed cell populations. These results suggest that care should be taken when administering this medication to animals with bacterial or viral infections, and we should avoid giving it to patients suffering from allergic or autoimmune disorders.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Street 13, 10-718 Olsztyn, Poland. tomasz.maslanka@uwm.edu.pl
authors.forename: Tomasz
authors.initials: T
authors.lastname: Maślanka
authors.forename: Jerzy Jan
authors.initials: JJ
authors.lastname: Jaroszewski
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018655:Lymphocyte Count; D000077239:Meloxicam; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D013843:Thiazines / Q000009:adverse effects*; D013844:Thiazoles / Q000009:adverse effects*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
chemical_list: D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; C086500:DMBT1 protein, Bos taurus; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013843:Thiazines; D013844:Thiazoles; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D003907:Dexamethasone; D007371:Interferon-gamma; D000077239:Meloxicam