Sex Differences and the Absence of Hepcidin in Post-Traumatic Anemia

Author(s):
Gwendolyn Gillies; Jennifer Munley; Lauren Kelly; Erick Pons; Kolenkode Kannan; Letitia Bible; Philip Efron; Alicia Mohr

Background:

Biologic sex is known to modulate inflammatory responses following critical illness and affect recovery from post-traumatic anemia. Hepcidin, an iron-regulating peptide hormone synthesized in the liver, is upregulated with inflammation and has been implicated in anemia after trauma and critical illness. The aim of this study was to investigate the impact of the absence of hepcidin on previously identified sex-specific differences in anemia recovery following critical illness.

Hypothesis:

We hypothesized that the absence of hepcidin would limit sex differences in recovery from post-traumatic anemia.

Methods:

Male and proestrus female hepcidin knockout (HAMP -/-) Sprague-Dawley rats (n=8-9/group) were subjected to lung contusion and hemorrhagic shock (LCHS) or LCHS with daily chronic restraint stress (LCHS/CS) and compared to naïve rodents. Hematologic data, bone marrow erythroid progenitor growth, and bone marrow transcription of ferroportin (FPN) and stem cell factor (SCF)were analyzed on day seven. Significance was defined as *p< 0.05.

Results:

On day 7, there was no significant difference in hemoglobin level between males and females in naïve, LCHS, or LCHS/CS HAMP -/- groups (Table). Change in hemoglobin and change in weight from day 0 to day 7 were not significantly different between males and females in LCHS or LCHS/CS HAMP -/- groups. Growth of colony forming unit-granulocyte, erythrocyte,monocyte,megakaryocyte (CFU-GEMM) was significantly higher in LCHS/CS HAMP -/- males compared to female counterparts on day 7 (Table). Bone marrow transcription of FPN and SCF was increased in LCHS HAMP -/- males compared to female counterparts on day 7.

Conclusions:

Following trauma with or without chronic stress, the absence of hepcidin did not prevent anemia in males or females. However, HAMP -/- males increased early erythroid progenitor colony growth and increased transcription of pro-erythroid factors FPN and SCF on day 7. Overall, these data suggest that the absence of hepcidin in males may have some benefit in recovery from post-traumatic anemia.