Plasma cytokine concentrations indicate that in vivo hormonal regulation of immunity is altered during long-duration spaceflight

Abstract

Aspects of immune system dysregulation associated with long-duration spaceflight have yet to be fully characterized and may represent a clinical risk to crewmembers during deep space missions. Plasma cytokine concentration may serve as an indicator of in vivo physiological changes or immune system mobilization. The plasma concentrations of 22 cytokines were monitored in 28 astronauts during long-duration spaceflight onboard the International Space Station. Blood samples were collected 3 times before flight, 3-5 times during flight (depending on mission duration), at landing, and 30 days after landing. Analysis was performed by bead array immunoassay. With few exceptions, minimal detectable mean plasma concentrations were observed at baseline (launch minus 180) for innate inflammatory cytokines or adaptive regulatory cytokines; however, interleukin (IL)-1ra and several chemokines and growth factors were constitutively present. An increase in the plasma concentration, tumor necrosis factor-α (TNFα), IL-8, IL-1ra, thrombopoietin (Tpo), vascular endothelial growth factor (VEGF), C-C motif chemokine ligand 2 (CCL2), chemokine ligand 4/macrophage inhibitory protein 1b (CCL4), and C-X-C motif chemokine 5/epithelial neutrophil-activating protein 78 (CXCL5) was observed associated with spaceflight. No significant alterations were observed during or following spaceflight for the inflammatory or adaptive/T-regulatory cytokines: IL-1α, IL-1β, IL-2, interferon-gamma (IFN-γ), IL-17, IL-4, IL-5, IL-10, G-CSF, GM-CSF, FGF basic, CCL3, or CCL5. This pattern of cytokine dysregulation suggests multiple physiological adaptations persist during flight, including inflammation, leukocyte recruitment, angiogenesis, and thrombocyte regulation.

FIG. 1.

Representative individual crewmember plasma cytokine concentrations during long-duration spaceflight. The graphs depict (A) IL-1ra, (B) IL-8, (C) CXCL5/ENA-78, (D) VEGF, (E) Tpo, (F) IL-6, (G) IL-1β, (H) TNFα, (I) IL-4. For all crewmembers, baseline concentrations (L-180) were normalized to zero, and deviations from baseline were plotted for all other time points. For all measured values below the assay sensitivity limit, the limit value itself was plotted. Statistically significant alterations in raw mean values are indicated (*) where P≤0.05; n=28.