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Introduction: Immune system dysrcgulation has been demonstrated to occur during and immediately following spaceflight. As the initial bias and magnitude for an immune response is heavily influenced by mono- cytelmacrophage secreted cytokines, this study investigated monocyte phenotype and cytokine production patterns following short-duration spaceflight. Methods: Secreted cytokine profiles were examined by cytometric bead array analysis of culture supernatants following whole blood culture activation with LPS or PMA+ionomycin. Nine short-duration Space Shuttle crewmernbers participated in this study. Results: Periph- eral monocyte percentages were unaltered postflight. Constitutive mono cyte expression of both CD62L and HLA-DR was reduced following spaceflight in a mission-specific fashion. Loss of either molecule indi- cates a functional disability of monocytes, either by inhibition of adhe- sion and tissue migration (CD62L) or by impaired antigen presentation (HLA-DR). Following LPS stimulation of monocytes, postflight expression of IL-6, TNFcs, and IL-10 were significantly reduced (by 43%, 44%, and 41%, respectively) and expression of IL-lb was elevated (65%). IL-8 pro- duction was either elevated or reduced in a mission-specific fashion. Following PMA+ionomycin stimulation of all leukocyte populations, only expression of IL-6 was significantly reduced postflight. Discussion: These data indicate that changes in monocyte constitutive phenotype and inflammatory cytokinc production occur following short-duration spaceflight, which may impact overall crewmember immunocompe- tence. Also, rnonocyte/macrophage function may be highly sensitive to mission specific parameters. [ABSTRACT FROM AUTHOR]

Introduction: As logistical access for space research becomes more limited and NASA prepares for exploration-class missions, ground-based spaceflight analogs will increase in importance for biomedical counter-measures development. A monitoring of immune parameters was performed during the NASA Flight Analogs Project bed rest study (without countermeasure); to establish `control' data against which future studies (with countermeasure) will be evaluated. Some of the countermeasures planned to he evaluated in future studies may impact immune function. Methods: The immune assessment consisted of: leukocyte subset distribution, early T cell activation, intracellular cytokine profiles, latent viral reactivation, virus specific T cell levels and function, stress hormone levels, and a behavioral assessment using stress questionnaires. Results: In general, subjects did not display altered peripheral leukocyte subsets, constitutive immune activation, altered T cell function, or significant latent viral reactivation (EBV, VZV). Levels of constitutively activated T cells (CD8+/CD69+) and virus-specific T cells (CMV and EBV) decreased during the study. Cortisol levels (plasma and saliva) did not vary significantly during 90-d bed rest. Conclusions: These data demonstrate the absence of significant immune system alteration and physiological stress during 90-d bed rest, and establish control data against which future studies (including countermeasures) may be compared. [ABSTRACT FROM AUTHOR]

Introduction: Immune system dysregulation has been demonstrated to occur during and immediately following spaceflight. If found to persist during lengthy flights, this phenomenon could be a serious health risk to crewmembers participating in lunar or Mars missions. Methods: A comprehensive postflight immune assessment was performed on 17 short-duration Space Shuttle crewmembers and 8 long-duration International Space Station (ISS) crewmembers. Testing consisted of peripheral leukocyte subset analysis, early T cell activation potential, and intracellular/secreted cytokine profiles. Results: For Shuttle crewmembers, the distribution of the peripheral leukocyte subsets was found to be altered postflight. Early T cell activation was elevated postflight; however, the percentage of T cell subsets capable of being stimulated to produce IL-2 and IFN-γ was decreased. The ratio of secreted lFN-γ:IL-10 following T cell stimulation declined after landing, indicating a Th2 shift. For the ISS crewmembers, some alterations in peripheral leukocyte distribution were also detected after landing. In contrast to Shuttle crewmembers, the ISS crewmembers demonstrated a statistically significant reduction in early T cell activation potential immediately postflight. The percentage of T cells capable of producing IL-2 was reduced, but IFN-γ percentages were unchanged. A reduction in the secreted lFNγ:IL-10 ratio (Th2 shift) was also observed postflight in the ISS crewmembers. Conclusion: These data indicate that consistent peripheral phenotype changes and altered cytokine production profiles occur following spaceflight of both short and long duration; however, functional immune dysregulation may vary related to mission duration. In addition, a detectable Th2 cytokine shift appears to be associated with spaceflight. [ABSTRACT FROM AUTHOR]