Anemia of chronic inflammation

Anemia is the condition of having either too few red blood cells or too little hemoglobin.  Hemoglobin is a protein found in red blood cells that transports oxygen.  Hemoglobin is one of the hemeproteins, meaning that it has an iron atom in the middle of a structural ring.  The iron allows hemoglobin to transport oxygen from the lungs to the capillaries, small blood vessels.  Thus, anemia can result in less than enough oxygen in the organs.  Iron status (how much iron a person has available for use) affects how well the body can oxygenate the tissues and generate energy.

Anemia is fairly common.  It is generally caused by blood loss, destroying too many blood cells (hemolysis) or not diminished hematopoiesis (the process of making red blood cells.)  Typical symptoms include weakness, fatigue, palness and shortness of breath.  More serious cases can cause heart palpitations, chest pain, fast heart rate and even heart failure.    There are many types of anemia.

One type of anemia is anemia of chronic disease, also called anemia of inflammatory response.  This type of anemia is seen in chronic illness.  In recent years, we have learned that this is most likely caused by overactivity of hepcidin, a hormone.  Hepcidin is the chief controller of iron levels in the body.  It can slow the body taking up iron from the diet and prevent iron from being released from its stores.

Overloading with iron will activate the body to make hepcidin.  This will result in a decrease in available iron, an increase of iron inside the cells that store it, and decreased absorption of iron in the gut.  Iron stores are composed mostly of cells in the reticuloendothelial system (RES), an older name for the mononuclear phagocyte system (MPS.)  These are cells that “eat” disease causing organisms, damaged cells or cellular debris, like macrophages.  Some of the cellular debris is pieces left over from broken down red blood cells, including heme.  Your body stores excess iron inside these cells to save for a time when it is needed. 

Your hepcidin level is regulated in response to many things, including anemia and inflammation.  Acute hemolysis, or destruction of red blood cells, from repeated blood draws decreased the amount of hepcidin your body made, even if the level was very high before.  This means that having blood drawn frequently signals to the body that it needs to keep its iron in its stores and shouldn’t take up any more from your diet.   

Acute inflammation decreases hepcidin, making iron more available.  But chronic inflammation increases hepcidin over 6X, making iron much less available to your body.  When your body is inflamed, its cells produce inflammatory molecules, like cytokines.  Some of these molecules, like IL-6, tell your liver to make more hepcidin.  If your body frequently sends out inflammatory signals, it can actually make it so that your cells are less able to release their iron.  It can also make your bone marrow less able to make red blood cells. 

When your body releases inflammatory cytokines, your body thinks it is fighting an infection.  These cytokines tell your body to make white blood cells, which your body thinks it needs to fight the infection.  White and red blood cells are made from the same stem cells in the bone marrow.  If the body is making more white cells, it is inherently making less red blood cells.  In this way, chronic inflammation increases the level of hepcidin, so the body keeps iron in its stores and stops absorbing additional iron, while also stimulating white blood cell production and decreasing red blood cell production. 

There are other ways in which decreased iron affects red blood cells, including interfering with the release of erythropoietin from the kidney.  This is the molecule that tells your bone marrow to make red blood cells.  When iron is deficient, the survival of red blood cells is also shorter.

So regardless of dietary iron intake, many people with chronic inflammation are functionally anemic.