Propranolol modulates androgen-expanded myeloid-derived suppressor cells (MDSC) in severely burned mice

Abstract

Abstract Severe burn injuries produce chronic hypermetabolic and hypercatabolic states persisting long after injury. For the improvement of net protein balance and lean body mass, we are trying to use oxandrolone (OX, a synthetic analog of testosterone) in severely burned patients subjected to the standard of care (SOC) including propranolol (PPL, a blocker of β-adrenergic receptors). OX has the potential to exacerbate post-burn immunoparalysis through the expansion of MDSC (Gr-1+CD11b+ cells). Since propranolol accelerates MDSC maturation, the effect of OX on the expansion of MDSC in severely burned mice subjected to SOC was studied. Mice were treated s.c. with OX (0.1 mg/kg, 1 and 12 h post burn) alone or in combination with PPL (3.3 mg/kg, 12 h post burn). MDSC in splenic MNC from these mice were analyzed by flow cytometry. Also, peritoneal Mϕ from these were analyzed for intracellular TNF-α, as an inhibitor of MDSC maturation. In the results, the number of MDSC increased 5.5-fold in burn mice treated with OX, as compared to that of MDSC in burned mice. However, this increase was not seen in burn mice treated with OX and PPL in combination. TNF-α+ cells increased 2.5-fold in the peritoneal Mϕ of burn mice treated with OX, but not in burn mice treated with OX and PPL. These results show that the number of MDSC is not increased by OX in severely burned mice treated with PPL.