Life Sciences & Biotechnology
Title : | Molecular mechanisms underlying gender dimorphism in the pathophysiology of Anemia of Inflammation in a rodent model |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Sudeshna Kar, Artemis Hospital, Haryana |
Timeline Start Year : | 2022 |
Timeline End Year : | 2025 |
Contact info : | Sudeshna.kar@artemishospitals.com |
Details
Executive Summary : | Anemia of Inflammation (AI) is the second most common cause of anemia worldwide and is linked to chronic infections and malignancies. AI arises from inflammation-driven abnormal iron sequestration and reduced iron availability for erythropoiesis. Immune-activated IL-6 induces hepatic hormone hepcidin, which in turn causes the degradation of iron transporter, ferroportin, leading to iron occlusion and reduced erythrocyte production. The hepcidin-ferroportin axis-mediated systemic hypoferremia also acts as an innate immune-defense mechanism by restricting essential iron from invading pathogens. There is a distinct gender disparity in immune responses against inflammatory stimuli, with males having more severe infections and weaker immune responses, while females have robust but persistent inflammatory responses. The hypothesis is that the gender dimorphism in immune responses to inflammatory stimuli extends to and converges with gender-linked disparity in inflammation-mediated defective iron metabolism and erythropoeisis in AI. Using a gain-of-function mutant of commensal E. coli and subclinical doses of LPS, researchers have established a recurrent low-grade inflammation model in rodents. Initial results showed AI-specific characteristics, including deficient hematological parameters, elevated levels of liver-restricted IL-6 and hepcidin induction, and higher estrogenic and subdued androgenic response in both genders. The study aims to investigate the interplay between inflammatory immune response, status of gonadal hormones, and changes in the hepatic-ferroportin axis, which drives gender-biased susceptibility to and manifestation of AI. |
Co-PI: | Dr. Surajit Ganguuly, Jamia Hamdard University, New Delhi-110062 |
Total Budget (INR): | 29,18,080 |
Organizations involved