Researchers at the Children’s Hospital of Philadelphia (CHOP) have discovered that tumor necrosis factor alpha (TNFα), a molecule typically associated with promoting inflammation, also plays a beneficial role in recovering from anemia caused by ongoing immune disturbances. This study was published in the journal Blood.
Anemia of inflammation (AI) is a condition where the body struggles to produce enough healthy red blood cells due to persistent inflammation. It is the second most common type of anemia worldwide after iron deficiency anemia and is prevalent among hospitalized and chronically ill patients. Causes include infections, autoimmune diseases, and cancers. Current strategies for addressing AI focus on treating the underlying disease, using transfusions in severe cases, and combining iron therapy with erythropoiesis-stimulating agents. Researchers aimed to better understand TNFα’s role in healing inflammation, which could lead to new therapeutic options.
“Our findings challenge the traditional view of TNFα as solely a harmful factor in anemia of inflammation,” said Amaliris Guerra, PhD, the study’s lead author and former post-doctoral fellow in CHOP’s Division of Hematology. “We demonstrated an essential role for TNFα in resolving the inflammatory response.”
In their preclinical study, researchers examined TNFα’s effects on hematopoietic stem cells (HSCs), responsible for generating all blood cells during and after inflammation. They found that without TNFα, HSCs did not recover properly, leading to prolonged anemia. The study showed that TNFα has a dual role: contributing to anemia during inflammation but necessary for recovery afterward.
“The implications of this research are significant for conditions characterized by chronic inflammation and anemia,” said Stefano Rivella, PhD, senior author and Kwame Ohene-Frempong Endowed Chair in Pediatric Hematology research at CHOP. “Our findings highlight the need for deeper investigations into the anti-inflammatory roles of TNFα.”
The researchers suggest further analysis of cytokines’ pro- and anti-inflammatory actions during AI could aid in developing treatments targeting AI across various conditions and offer new management options for patients unsuitable for anti-TNFα therapy.
Guerra et al.’s paper titled “TNFα signaling restores steady-state hematopoiesis in anemia of inflammation TNFαKO mouse” can be found in Blood.
