Abstract
Since the first Apollo mission in 1969, microgravity has been linked to many alterations of astronauts’ physiology, among which immunosuppression, altered inflammation and bone loss represent relevant examples. In the past 40 years, extensive investigations have been conducted in order to characterize the molecular mechanisms driving the alterations caused by prolonged weightlessness on human health. However, almost all studies eluded the role played by bioactive lipids, a vastly heterogeneous class of endogenous molecules, which, under normal conditions, control immune and bone homeostasis. This is somewhat surprising, because it is widely accepted that pathological derangement of the production or signalling of these endogenous compounds leads to the onset and/or progression of numerous diseases. In particular, eicosanoids and endocannabinoids are known to play a role in immune responses and bone remodelling. Both classes represent the only lipids as yet investigated in Space, and are increasingly recognised as promising therapeutic candidates to combat different human disorders. This review summarizes evidence gathered in the past two decades on the changes in these two pivotal lipid signalling systems, through both simulated and authentic weightlessness (i.e., on board the International Space Station and in parabolic flights).
Highlights
Microgravity in Human HealthThe first evidence for the presence of pathophysiological alterations associated with microgravity was published in 1975, with the observation that 15 out of 29 of the Apollo mission’s astronauts displayed increased viral or bacterial infections [1]
Faculty of Biosciences and Technology for Food Agriculture and Environment, University of Teramo, European Center for Brain Research/IRCCS Santa Lucia Foundation, Via del Fosso di Fiorano 64, Department of Medicine, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy
A dynamic bone remodelling results from the balance between deposition and resorption of hydroxyapatite mineral matrix, regulated by bone-resident osteoblasts and osteoclasts, respectively. This balance is regulated both remotely through the parathormone/calcytonine axis, which modulates osteoblasts and osteoclasts, and locally through osteocytes embedded in the mineral matrix that act as mechanosensors, translating the compressive forces exerted by gravity on the tissue into biological and hormone-like signals that participate in bone homeostasis [51]
Summary
The first evidence for the presence of pathophysiological alterations associated with microgravity was published in 1975, with the observation that 15 out of 29 of the Apollo mission’s astronauts displayed increased viral or bacterial infections [1]. The alteration of the adaptive immune response exerted by microgravity might have many implications, in that a recent work used a mouse in vivo model to demonstrate that Space flight impairs immune tolerance by significantly enhancing the production of inflammatory cytokines, such as INF-γ and IL-17, the latter molecule being engaged in the pathogenesis of a number of autoimmune conditions [36,37]. This effect seemingly depends on the depletion of T regulatory (Treg) cells through the repression of the IL-2/CD25 axis [37]. The latter molecules represent the fulcrum of the immune response, governing the initiation, extent and outcome of the inflammatory event, and understanding their role in the modifications elicited by microgravity on human immune networks represents a crucial piece of the puzzle that will allow safe Space travel in the near future
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