Page 158 - Helicobacter pylori and Gastric Cancer: From Tumor microenvironment to Immunotherapy

Effects of space flight-associated microgravity on erk activation.
Although less pronounced than the effect on Jun-N-terminal kinase, inhibitory influence of microgravity on the capacity of LPS to provoke activation of the extracellular regulated kinase (ERK) was observed[69]. This corresponds with recent findings in T cells that show a minor effect of microgravity on ERK phosphorylation in unstimulated T cells[76]. Thus, the impact of microgravity is not solely restricted to the Jun-N-terminal kinase. Diminished activity of the immune system is among the foremost effects of space flight on the human body[77]. Importantly, this reduced activity of the immune system is well-tolerated. Over forty years of experience with manned space flight have now conclusively demonstrated that man can easily survive and work in weightless conditions, despite the chronic repression of the body’s immune functions[78].
This suggests that mimicking space-related immunosuppression on earth may be a fairly safe way of suppressing the action of the immune system. Although experimental requirements allowed for only 6 minutes of microgravity, there is good evidence that even a relatively short inhibition of kinases can have a substantial effect on the functionality of the innate immune system[79]. Therefore we feel that the observed effect on Jun-N-terminal kinase is relevant to the explanation of space flight-associated immunosuppression. The marked dichotomy between p38 MAP kinase and Jun-N- terminal kinase is consistent with these observations: p38 MAP kinase is essential for fighting immediate bacterial threats, and thus its inhibition causes undesirable side effects in these and other respects[80]. On the other hand, the Jun-N-terminal kinase is more associated with chronic inflammatory responses[81, 82] whose inhibition represents a clear and for now unresolved clinical need.
Conclusion and future direction.
Immune system of space travellers diminishes upon spaceflight. Importantly, although this reduced activity of the immune system is likely to become a problem concerning the more extended missions currently being planned (especially a manned mission to Mars may yield specific challenges in this regard), space-related immunosuppression is
Chapter 7
152
156