Effects of isolated, confined and extreme environments on parameters of the immune system - a systematic review

Abstract

Background: The immune system is a crucial part of the body's defense against infection and disease. However, individuals in antigen-limited environments face unique challenges that can weaken their immune systems. This systematic review aimed to investigate the impact of an exposure to an isolated, confined and extreme (ICE) environment with limited antigen diversity on human immune parameters.

Methods: A systematic literature search was conducted using PubMed, Web of Science and Cochrane Library to identify relevant studies on immune system parameters in ICE environments. The studies were grouped by ICE type (space missions, microgravity simulations like bed rest studies, space simulation units like MARS500, and Antarctic research stations) to allow for clearer comparison and analysis of immune outcomes.

Results: Analysis of 140 studies revealed considerable heterogeneity in study designs and outcomes, reflecting the complexity of immune responses across ICE environments. Nevertheless, immune dysregulation was consistently observed across environments. Space missions and Antarctic stations, in particular, showed pronounced immune changes, likely due to low antigen diversity and extreme conditions, with higher rates of infections and allergic responses suggesting increased vulnerability. Space simulation units exhibited immune changes similar to those in actual space missions, while gravity simulation studies, which focus on fluid shifts and bone loss, showed fewer immune alterations. Across environments, most immunological measures returned to baseline after isolation, indicating resilience and the potential for recovery upon re-exposure to diverse antigens.

Conclusion: Reduced antigen diversity in ICE environments disrupts immune function, with effects often compounded by extreme conditions. Although immune resilience and recovery post-isolation are promising, the heterogeneity in current studies highlights the need for targeted research to identify specific immune vulnerabilities and to develop countermeasures. Such measures could reduce immune-related health risks for individuals in isolated settings, including astronauts, polar researchers, and vulnerable populations on Earth, such as the elderly or immunocompromised, thereby enhancing resilience in confined environments.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023476132.

Keywords: ICE environments; antigen diversity; antigen-limited environments; bed rest; immune dysregulation; immune system; resilience; space analogues.

Figure 1

PRISMA Flow chart of the included studies. Note: The search was conducted on 22^nd of November 2022 (PubMed n = 1,943; Web of Science n = 2,778; Cochrane Library n = 217) and updated on 28^th of January 2025 (results in the figure). The search term for the Cochrane Library was adjusted to the updated Cochrane search criteria. However, the search on 28^th of January 2025 yielded only 210 studies in total, of which 38 were newly identified compared to the initial search. The included studies were categorized based on their respective habitats. A total of 140 studies were included in the quantitative analysis. Three of these studies covered multiple habitats and are therefore counted in more than one group category. The numbers in parentheses indicate the count after adjusting for these overlaps.

Figure 2

Immune response profile (% reports) at different time points, classified by ICE condition. The diagram illustrates the percentage of studies reporting effects on various immunological parameters—categorized as increase (↑, orange), decrease (↓, blue), or stability (↔, grey)—across three time points: pre- vs. during isolation, during vs. post isolation, and pre- vs. post isolation. For clarity, only immune parameters with a ≥5% reporting frequency were included; unchanged parameters are not shown. anti, anti-inflammatory; B, B-cells; C, Complement component; Cy, Cytokines; Eos, Eosinophils; GM-CSF, Granulocyte Macrophage Colony-Stimulating Factor; Gra, Granulocytes; Ig, Immunoglobulin; IL, Interleukin; IFN, Interferon; Leu, Leukocytes; Lymp, Lymphocytes; Lys, Lysozyme; MCP, Monocyte Chemoattractant Protein; MIP, Macrophage Inflammatory Protein; Mo, Monocytes; NK, Natural Killer cells; Neu, Neutrophils; Phag, Phagocytes; RANTES, Regulated on Activation, Normal T cell Expressed and Secreted; T, T-cells; TGF, Transforming Growth Factor; TNF, Tumor Necrosis Factor.

Figure 3

Effects of normoxic and hypoxic conditions on immunological parameters. Bar chart illustrating the reported effects in immunological parameters (% of all reported effects) within terrestrial habitats under normoxic and hypoxic conditions, categorized by their occurrence pre/during, during/post, and in pre/post comparison of mission periods. The chart quantifies the percentage of studies noting an effect (dark grey), and no change (light grey) in immunological responses.

Figure 4

Similarities in absolute values between the ICE conditions. Similarity means that either all studies indicated the same direction (increase, decrease or unchanged) or the majority of studies indicated the same direction.

Figure 5

Summary of reported health outcomes across different habitats in all studies. This visualization presents a comparative analysis of health outcomes, illustrating the varying frequencies of reported infections, allergic reactions, and medication use across diverse environmental conditions. Larger red points indicate higher reporting frequencies, while smaller blue points represent lower frequencies. The calculation of symbol size refers to the row. Studies that made no mention of health-related outcomes were excluded from this representation.

Figure 6

Risk of bias analysis, summary plot.