Multiple interleukin-2 signaling pathways differentially regulated by microgravity.

Defects in innate immunity have been demonstrated in astronauts after space flight. To investigate the role of microgravity on innate immune function, we evaluated NK and LAK activity of human PBMC stimulated with IL-2 under conditions of simulated microgravity, by using a rotating wall vessel (RWV) culture system. Under these conditions, both NK and LAK activity were generated at levels comparable to those found in static flask cultures. The phenotype of the activated PBMC was similar between the two culture conditions, with one notable exception: the IL-2 receptor alpha chain (CD25), which failed to be upregulated in simulated microgravity. To further investigate this change in IL-2 signaling, we examined the ability of IL-2 to induce secondary cytokines. The production of IFNgamma, IL-1beta, and TNFalpha was almost completely abrogated in the microgravity cultures, suggesting that the IL-2 signaling pathways leading to various IL-2-mediated effects are differentially regulated under bioreactor culture conditions.