Page 152 - Helicobacter pylori and Gastric Cancer: From Tumor microenvironment to Immunotherapy

Firstly, how to balance natural microbiota diversity during long term stay in space. Secondly, how can we combine a low pathogenic environment for the crew of a space craft without altering the normal composition of the commensal flora. Third, how can we restore normal gut flora after partial eradication by for example antibiotic treatment. And lastly, to what extend does cosmic radiation damage the diversity of the microbiome.[51].
Altered cytokine production does not provide a mechanical explanation for microgravity-induced immune suppression.
Clinical strategies to interfere with the human immune system can involve either change in the extracellular or modification of cellular biochemistry operative in the immune effector cell. Examples of the former like the modification of cellular biochemistry by increasing the blood concentration of immunosuppressive corticoids[52] or the bio-neutralization of pro-inflammatory cytokine Tumour Necrosis Factor[53] by intravenous administration of anti-TNF antibodies are used with great therapeutic success in the treatment of autoimmune disease. An example of the latter is inhibition of Ca2+ transient-dependent activation of immune effector cells by cyclosporin-like compounds in transplantation medicine [54]. The effects of microgravity on immunity could be derived alternatively from altered cytokine production, thus altering the extracellular environment in which an immune response has to develop, or from autonomous cell mechanisms, in which the cellular response to extracellular cues is changed. The experiments with stimulation of ex vivo T cells would point to the latter; such reactions do in general not prominently involve alterations in cytokine milieu. Indeed, work in bone suggests that levels of immunosuppressive cytokines like TGF-ß are decreased instead of increased during microgravity and thus unlikely to account for space-related immunosuppression[30]. In agreement with the notion apparently that the effects of microgravity are cell-intrinsic rather than the consequence of an altered cytokine milieu, is the observation that in primary isolated rat lymphocytes, leptin (a hormone that famously regulates appetite[55], but is also prominent regulator of immunological[56] and histo-static[57] functions in the endodermal mucosal compartments) loses its capacity to stimulate proliferation under simulated microgravity[27]. Also efforts to measure the concentrations of cytokines and other immunologically relevant hormones in the peripheral blood of astronauts or experimental space-going rodents have never yielded convincing reductions in the profile of these humoral factors (e.g. Miller et al. J. Appl. Physiol. 78: 810-813), although also during investigations under conventional 1xg
Chapter 7
Chapter 7
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