Risk of Crew Adverse Health Event Due to Altered Immune Response
Determining the effect of space travel on the human immune system has proven to be extremely challenging. Limited opportunities for in-flight studies, varying mission durations, technical and logistical obstacles, small subject numbers, and a broad range of potential assays have contributed to this problem. Additionally, the inherent complexity of the immune system, with its vast array of cell populations, sub-populations, diverse regulatory molecules, and broad interactions with other physiological systems, makes determining precise variables to measure very difficult. There is also the challenge of determining the clinical significance of any observed immune alterations. Will such a change lead to disease, or is it a transient subclinical observation related to short-term stress? The effect of this problem may be observed by scanning publications associated with immunity and spaceflight, which began to appear during the 1970s. Although individually they are each valid studies, the comprehensive literature to date suffers from widely varying sampling methods and assay techniques, low subject counts, and sometimes a disparate focus on narrow aspects of immunity. The most clinically relevant data are derived from in-flight human studies, which have demonstrated altered cell-mediated immunity and reactivation of latent herpes viruses. Much more data are available from post-flight testing of humans, with clear evidence of altered cytokine production patterns, altered leukocyte distribution, continued latent viral reactivation, and evidence of dramatically altered virus-specific immunity. It is unknown if post-flight assessments relate to the in-flight condition or are a response to landing stress and readaptation. In-flight culture of cells has clearly demonstrated that immune cells are gravity-sensitive and display altered functional characteristics. It is unknown if these data are related to in vivo immune cell function or are an artifact of microgravity culture. Ground analog testing of humans and animals, as well as microgravity-analog cell culture, has demonstrated utility. However, in all cases, it is not known with certainty if these data would reflect similar testing during space travel. Given their ready availability, ground analogs may be extremely useful for assay development and the evaluation of potential countermeasures. In general, the evidence base suffers from widely disparate studies on small numbers of subjects that do not directly correlate well with each other or spaceflight itself. Also lacking are investigations of the effect of gender on adaption to spaceflight. This results in significant knowledge 'gaps' that must be filled by future studies to completely determine any clinical risk related to immunity for human exploration-class space missions. These gaps include a significant lack of in-flight data, particularly during long-duration space missions. The International Space Station represents an excellent science platform with which to address this knowledge gap. Other knowledge gaps include lack of a single validated ground analog for the phenomenon and a lack of flight-compatible laboratory equipment capable of monitoring astronauts (for either clinical or research purposes). However, enough significant data exist, as described in this manuscript, to warrant addressing this phenomenon during the utilization phase of the ISS. A recent Space Shuttle investigation has confirmed the 31 in-flight nature of immune dysregulation, demonstrating that it is not merely a post-flight phenomenon. Several current studies are ongoing onboard the ISS that should thoroughly characterize the phenomenon. NASA recognizes that if spaceflight-associated immune dysregulation persists during exploration flights in conjunction with other dangers, such as high-energy radiation, the result may be a significant clinical risk. This emphasizes the need for a continued integrated comprehensive approach to determining the effect of prolonged spaceflight, separated from transient launch and landing stresses, on human immunity. After such studies, the phenomenon will be understood, and, hopefully, a monitoring strategy will have been developed that could be used to monitor the effectiveness of countermeasure