Substance P effects on developing thymocytes in hindlimb unloaded rats

Introduction: The purpose of this study was to examine the effects of substance P (SP) on the immune system in a condition similar to microgravity. We analyzed immune disturbances caused by subjecting Fischer 344 rats to a 45° antiorthostatic suspension technique, otherwise known as the hindlimb unloading (HU) model. Methods: Four groups of rats were assigned to either the prone control non-substance P group (P-NSP), prone control substance P group (P-SP), hindlimb unloaded non-substance P (HU-NSP) or the hindlimb unloaded substance P group (HU-SP). SP was administered at 10 ml of a 1 μmol·L^-1 concentration for 15 min·d^-1. HU and SP exposure for all groups lasted 16 d. After 16 d, 500 μl of blood was obtained to assay for both T-cell phenotype and corticosterone (CS) levels. Thymus lobes were excised in order to examine T-cell phenotype. Thymocytes were counted and stained for lymphocyte markers (CD4, CD8, and CD3). An analysis of variance (ANOVA) test was used to determine significance between groups (p ≤ 0.05). Results: HU-NSP rats showed a decrease in thymic CD4+CD84-cells from 85.51 ± 1.9% to 62.06 ± 1.9% when compared with P-NSP rats. SP reversed these effects and returned CD4+CD8+ cells to control levels (76.60 ± 1.9%). Discussion: Daily SP treatment was found to reverse the deleterious effects caused by HU and corticosterone in rat thymic immune cells. SP could prove to be an effective means for keeping the immune system functioning at normal levels in microgravity, allowing astronauts to stay in space longer and maintain a more productive immune system.