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 degrees 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 micromol x L(-1) concentration for 15 min x d(-1). HU and SP exposure for all groups lasted 16 d. After 16 d, 500 microl 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 < or = 0.05). RESULTS: HU-NSP rats showed a decrease in thymic CD4+CD8 +/- 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.

Changes in organ perfusion and weight ratios in post-simulated microgravity recovery.

Head-down tilt models have been used as ground-based simulations of microgravity. Our previous animal research has demonstrated that there are significant changes in fluid distribution within 2 h after placement in a 45 degrees head-down tilt (45HDT) position and these changes in fluid distribution were still present after 14 days of 45HDT. Consequently, we investigated changes in fluid distribution during recovery from 16 days of 45HDT. Changes in radioactive tracer distribution and organ/body weight ratio were examined in rats randomly assigned to a 45HDT or prone control group. The 45HDT rats were suspended for 16 days and then allowed to recover at the prone position 0, 77, 101, or 125 h post-suspension. Animals were injected with technetium-labeled diethylenetriamine pentaacetate (99mTcDTPA, MW=492 amu, physical half-life of 6.02 h) and then killed 30 min post-injection. Lungs, heart, liver, spleen, kidneys, and brain were harvested, weighed, and measured for radioactive counts. Statistical analyses included two-way analysis of variance (ANOVA) that compared 45HDT versus controls at the four experimental time points. The organ weight divided by the body weight ratio for the brain, heart, kidneys and liver in the 45HDT rats was significantly different than the control rats, regardless of time (treatment). There was no difference between the different time points (time). The average 99mTcDTPA count divided by the organ weight ratio values for the heart, liver, and spleen were significantly higher in the 45HDT group than the control group. The average counts for the heart and spleen were significantly higher at 77, 101, and 125 h than at time zero. We conclude that the major organs have different recovery patterns after 45HDT for 16 days in the rat.