Immunomodulatory Effects of the Cyclooxygenase Inhibitor Lornoxicam on Phenotype and Function of Camel Blood Leukocytes.

Abstract

Simple SummaryThe present study investigated the immunomodulatory effects of the unspecific cyclooxygenase inhibitor lornoxicam on the immunophenotype and some functions of dromedary camel blood leukocytes. Intravenous injection of camels with a single dose of lornoxicam induced a significant change in the camel leukogram, which is characterized by reduced cell numbers of all leukocyte subpopulations. In vitro analysis of cell vitality revealed a pro-apoptotic effect of lornoxicam on camel leukocytes, which may be responsible for the lornoxicam-induced leukocytopenia in vivo. Functional ex vivo and in vitro analysis of the key antimicrobial functions, phagocytosis and ROS production indicates inhibitory effects of lornoxicam on the antimicrobial capacity of the blood phagocytes, monocytes and neutrophils. Furthermore, lornoxicam induced an anti-inflammatory phenotype of monocytes, characterized by reduced expression of major histocompatibility complex (MHC) class II molecules and increased expression of CD163 molecules. The present study identified for the first time inhibitory effects of the COX-inhibitor lornoxicam on some phenotypic and functional properties of camel blood immune cells and recommends considering these effects when using lornoxicam in camel medicine.(1) Background: Lornoxicam is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic, antiphlogistic and antipyretic effects. The improved tolerance of lornoxicam due to the relatively shorter elimination half-life in comparison to other members of the oxicams may favor its application in the management of pain and inflammation in race dromedary camels. There are no studies conducted yet on the immunomodulatory or immunotoxilogic effect of lornoxicam in camels. Therefore, the current study aimed to evaluate the immunomodulatory effects of the cyclooxygenase inhibitor lornoxicam on some phenotypic and functional properties of camel blood leukocytes; (2) Methods: Using flow cytometry, blood leukocyte composition, monocyte phenotype, and antimicrobial functions of neutrophils and monocytes were analyzed ex vivo after a single dose injection with lornoxicam. In addition, the effect of in vitro incubation of camel blood with lornoxicam on leukocyte cell vitality and antimicrobial functions were evaluated; (3) Results: The injection of camels with a single dose of lornoxicam resulted in a significant change in their leukogram with reduced numbers of total leukocytes, neutrophils, eosinophils, monocytes, and lymphocytes. Within the lymphocyte population, the numbers of CD4+ T cells, γδ T cells, and B cells decreased significantly in blood after injection of camels with lornoxicam. In addition, injection of lornoxicam resulted in decreased abundance of major histocompatibility complex (MHC) class II molecules and increased abundance of the scavenger receptor CD163 on blood monocytes, indicating an anti-inflammatory phenotype of monocytes. Functionally, administration of lornoxicam decreased the capacity of camel neutrophils and monocytes to uptake bacteria and to produce reactive oxygen species (ROS) after bacterial stimulation. Similarly, the in vitro whole blood incubation with lornoxicam resulted in reduced phagocytosis and ROS production activity of the camel blood phagocytes. Flow cytometric analysis of cell vitality, including cell necrosis and apoptosis, revealed a pro-apoptotic effect of lornoxicam on camel leukocytes; (4) Conclusions: Lornoxicam administration, at the dose and intervals utilized herein, induces significant changes in the phenotype and function of camel blood leukocytes. The reduced cell numbers of all studied leukocyte subpopulations in lornoxicam-treated camels, which seems to be a result of enhanced cell apoptosis, indicates an inhibitory effect rather than a modulatory effect of lornoxicam on the camel immune system, which need to be considered when using lornoxicam in camel medicine.