The science behind Neupogen

If you’re on a strong chemotherapy, you may be required to take Neupogen to help boost the production of your white blood cells. But, how exactly does this drug work? Dr Nicole Holland sheds some light on the process.

WHAT IS NEUPOGEN?

Neupogen is recombinant granulocyte-colony stimulating factor (G-CSF), a drug that enhances the production of neutrophils. The body makes a natural protein called G-CSF, which acts in the bone marrow to boost the production of these white blood cells called neutrophils. During chemotherapy, your bone marrow and white blood cells can be suppressed which puts you at risk of infection. Neupogen can help reverse this.

The mature cells present within the blood are produced by precursors which are resident in the bone marrow. Blood cells have diverse functions – red blood cells are responsible for oxygen transport, platelets are involved in clotting, and the white blood cells are the effector cells of the immune system.

Different stimuli result in the manufacture and release of particular types of blood cells. The signal which triggers production is typically a chemical messenger or a particular cocktail of chemicals. Many of these substances are now used therapeutically, when a boost in the numbers of a target cell type is required.

Granulocyte-colony stimulating factor (G-CSF) is one of the proteins made by your body to stimulate cell proliferation. Neupogen is a form of G-CSF – recombinant granulocyte-colony stimulating factor – a drug that enhances the production of neutrophils.

Neutrophils are typically the most numerous white blood cells in the peripheral blood. They’re the ‘patrolling soldiers’ that can ingest and destroy foreign organisms such as bacteria. Their ability to kill bacteria relies on the production of free radicals and certain degrading enzymes. Neutrophils are short-lived cells. When there is a threat to the host, their numbers have to increase rapidly and they need to be quickly transported to the site of infection. The expression of various adhesion molecules on their cell surface and their amoeboid motility allows them to exit the blood stream at the site of inflammation.

Neutropenia – a decrease in the neutrophil count  – or impaired neutrophil function results in increased susceptibility to infection, particularly bacterial infection, and can vary from mild to severe. While a mild neutropenia may not require any intervention, severe neutropenia can be life-threatening. Bacteria and fungi are present on our skin and mucous membranes; a breach in the integrity of these barriers can have serious consequences in a neutropenic patient.

Neupogen is produced using DNA technology which allows the manufacture of large amounts of protein analogous to human G-CSF. G-CSF is a glycoprotein growth factor which following binding to its specific receptor on target cells, promotes the proliferation and maturation of neutrophils, as well as their functional activation.

In the clinical setting, Neupogen is frequently used as an adjunct to chemotherapy. Many chemotherapeutic agents are designed to destroy actively dividing cells, as cancer cells tend to have a high proliferation rate. As a consequence, certain normal cells which have a high turnover, such as those of the bone marrow, are also targeted. Effective treatment of cancer requires management of these side effects. Neupogen – to stimulate neutrophil production – and blood products, such as red cell and platelet transfusions, are used to reduce the consequences of the bone marrow suppression caused by chemotherapy.

In addition, Neupogen increases the peripheral blood white cell count and allows the mobilisation of stem cells which are harvested for stem cell transplants.

Certain people are born with a low neutrophil count or develop neutropenia during their lifetime, e.g. patients with aplastic anaemia. Growth factor therapy is also utilised to increase the neutrophil count in these settings. The effect of Neuopogen is not limited to neutrophil stimulation. Many growth factors have overlapping functions, and Neupogen has been used with erythropoietin (a red cell growth factor) to treat anaemia in certain clinical contexts.

Together with the therapeutic benefits comes the risk of side effects. Allergic reactions have been described. One of the more commonly reported effects with administration is bone pain which may be a result of the expanding bone marrow. There has been a theoretical concern about stimulating malignant cells as well as normal marrow stem cells.

The increased understanding of the body’s functioning and the role of growth factors has allowed us to harness their use therapeutically. Neupogen has been used in many clinical scenarios and has significantly improved the outcome of chemotherapy.

Written by Dr Nicole Holland.

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