Stimulatory action of cyclooxygenase inhibitors on hematopoiesis: a review.

Michal Hofer,Zuzana Hoferová,Denisa Komůrková,Milan Pospíšil,Lenka Weiterová

doi:10.3390/molecules17055615

Abstract

The presented review summarizes experimental data obtained with a mouse model when investigating the relationship between inhibition of prostaglandin production and hematopoiesis. While prostaglandin E2 acts in a negative feedback control of myelopoiesis, inhibition of cyclooxygenases, responsible for its production, shifts the feedback to positive control. Based on these relationships, agents inhibiting cyclo-oxygenases, known as non-steroidal anti-inflammatory drugs (NSAIDs), can activate hematopoiesis and be protective or curative under myelosuppressive states. The effectiveness of therapeutic use of NSAIDs in these situations is expressive especially under the selective inhibition of cyclooxygenase-2 (COX-2), when undesirable side effects of cyclooxygenase-1 inhibition, like gastrointestinal damage, are absent. The effects of the clinically approved selective COX-2 inhibitor, meloxicam, were investigated and demonstrated significant hematopoiesis-stimulating and survival-enhancing actions of this drug in sublethally or lethally γ-irradiated mice. These effects were connected with the ability of meloxicam to increase serum levels of the granulocyte colony-stimulating factor. It can be inferred from these findings that selective COX-2 inhibitors might find their use in the treatment of myelosuppressions of various etiologies.

Highlights

Hematopoiesis is an intricate complex of processes through which functional blood cells of several lineages are produced
The administration of indomethacin, a drug belonging to the non-steroidal anti-inflammatory drugs (NSAIDs) class and acting on the principle of non-selective inhibition of cyclooxygenases, was observed to induce mouse splenic erythropoiesis and to increase numbers of granulocyte-macrophage progenitor cells in bone marrow [8]
The results of the studies on the action of the selective inhibitor of cyclooxygenase-2, meloxicam, clearly show that this drug retains the hematopoiesis-stimulating effects of the classical NSAIDs but shows much less undesirable side effects and, they strongly suggest the possibility of its use in the treatment of radiation-induced myelosuppression

Summary

Introduction

Hematopoiesis is an intricate complex of processes through which functional blood cells of several lineages are produced These processes take place in hematopoietic tissues which are a compartmentalized system of cells undergoing proliferation and differentiation during their development from stem cells through progenitor and precursor cells resulting in production of mature blood cells. These findings seem to be in contradiction to numerous findings on suppressor effects of PGE2 on hematopoiesis and on hematopoiesis-stimulating action of cyclooxygenase inhibitors Their explanation in connection with the reported stimulatory effects of NSAIDs may consist in the fact that the hematopoietic stem cells compartment does not play a determinant role in the time period of the lowest hematopoietic depression following a myelo-suppressive intervention. Experimental and clinical data demonstrate a reduced risk of the undesirable gastrointestinal side effects after administration of COX-2-selective inhibitors as compared with the effects induced by classical non-selective cyclooxygenase inhibitors [22]

Action of Non-Selective Cyclooxygenase Inhibitors on Hematopoiesis

Action of Selective Cyclooxygenase-2 Inhibitors on Hematopoiesis

Notes on the Use of Meloxicam in Anti-Tumor Therapy in Connection with Its

Conclusions