Researchers at Children’s Hospital of Philadelphia (CHOP) found compelling preclinical evidence that a molecule called tumor necrosis factor alpha (TNFα), typically known for promoting inflammation, also plays a helpful role in recovery from anemia that is caused by ongoing immune disturbances. The research was published today in the journal Blood.
Anemia of inflammation (AI) is a common condition where the body has trouble making enough healthy red blood cells because of ongoing inflammation. AI is the second most prevalent anemia worldwide after iron deficiency anemia and the most common anemia among hospitalized and chronically ill patients. Causes of AI include microbial pathogen infections, systemic autoimmune diseases and cancers. Strategies to address AI typically focus on treating the underlying disease, using transfusion in severe and/or symptomatic cases, and combining iron therapy with erythropoiesis-stimulating agents. Due to reports of improvements in anemia in patients who have diseases with chronic inflammation, researchers sought to better understand TNFα’s role in healing inflammation, which may open the door to new therapeutic avenues.
“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, a former post-doctoral fellow in the Division of Hematology at CHOP. “We demonstrated an essential role for TNFα in resolving the inflammatory response, introducing a new model to investigate the role of TNFα in the etiology of AI. We also provide potential clues for exacerbations and, yet unexplained side effects in some patients treated with TNFα inhibitors.”
In the preclinical study, researchers observed the effects of TNFα on hematopoietic stem cells (HSCs), which are responsible for generating all blood cells, during and after inflammation. They discovered that in the absence of TNFα, HSCs failed to recover properly, leading to prolonged anemia and collapse of hematopoiesis. They then demonstrated through additional modeling that TNFα plays a dual role – it contributes to anemia during inflammation but is also necessary for recovery afterwards.
“The implications of this research are significant for conditions characterized by chronic inflammation and anemia,” said Stefano Rivella, PhD, a senior author, the Kwame Ohene-Frempong Endowed Chair in Pediatric Hematology research and faculty member in the Division of Hematology at CHOP. “Our findings highlight the need for deeper investigations into the anti-inflammatory roles of TNFα and associated pathways to develop alternative anti-TNFα therapies and/or combination approaches to treat autoimmune disorders.”
The researchers noted that further nuanced analysis of the pro- and anti-inflammatory actions of cytokines during AI would aid both in the translational development of agents to mechanistically target AI in numerous conditions, as well as provide new options for the management of patients who are not candidates for anti-TNFα therapy.
Guerra et al. “TNFα signaling restores steady-state hematopoiesis in anemia of inflammation TNFαKO mouse.” Blood. June 13, 2025. DOI 10.1182/blood.2025029352
Featured in this article
Experts
Specialties & Programs
Researchers at Children’s Hospital of Philadelphia (CHOP) found compelling preclinical evidence that a molecule called tumor necrosis factor alpha (TNFα), typically known for promoting inflammation, also plays a helpful role in recovery from anemia that is caused by ongoing immune disturbances. The research was published today in the journal Blood.
Anemia of inflammation (AI) is a common condition where the body has trouble making enough healthy red blood cells because of ongoing inflammation. AI is the second most prevalent anemia worldwide after iron deficiency anemia and the most common anemia among hospitalized and chronically ill patients. Causes of AI include microbial pathogen infections, systemic autoimmune diseases and cancers. Strategies to address AI typically focus on treating the underlying disease, using transfusion in severe and/or symptomatic cases, and combining iron therapy with erythropoiesis-stimulating agents. Due to reports of improvements in anemia in patients who have diseases with chronic inflammation, researchers sought to better understand TNFα’s role in healing inflammation, which may open the door to new therapeutic avenues.
“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, a former post-doctoral fellow in the Division of Hematology at CHOP. “We demonstrated an essential role for TNFα in resolving the inflammatory response, introducing a new model to investigate the role of TNFα in the etiology of AI. We also provide potential clues for exacerbations and, yet unexplained side effects in some patients treated with TNFα inhibitors.”
In the preclinical study, researchers observed the effects of TNFα on hematopoietic stem cells (HSCs), which are responsible for generating all blood cells, during and after inflammation. They discovered that in the absence of TNFα, HSCs failed to recover properly, leading to prolonged anemia and collapse of hematopoiesis. They then demonstrated through additional modeling that TNFα plays a dual role – it contributes to anemia during inflammation but is also necessary for recovery afterwards.
“The implications of this research are significant for conditions characterized by chronic inflammation and anemia,” said Stefano Rivella, PhD, a senior author, the Kwame Ohene-Frempong Endowed Chair in Pediatric Hematology research and faculty member in the Division of Hematology at CHOP. “Our findings highlight the need for deeper investigations into the anti-inflammatory roles of TNFα and associated pathways to develop alternative anti-TNFα therapies and/or combination approaches to treat autoimmune disorders.”
The researchers noted that further nuanced analysis of the pro- and anti-inflammatory actions of cytokines during AI would aid both in the translational development of agents to mechanistically target AI in numerous conditions, as well as provide new options for the management of patients who are not candidates for anti-TNFα therapy.
Guerra et al. “TNFα signaling restores steady-state hematopoiesis in anemia of inflammation TNFαKO mouse.” Blood. June 13, 2025. DOI 10.1182/blood.2025029352
Contact us
Jennifer Lee
Division of Hematology