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 NR 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 gene rated at levels comparable to those found in static flask cultures. The phe notype of the activated PBMC was similar between the two culture conditions , with one notable exception: the IL-2 receptor or chain (CD25), which fail ed to be upregulated in simulated microgravity. To further investigate this change in IL-2 signaling, we examined the ability of IL-2 to induce second ary cytokines. The production of IFN gamma, IL-1 beta, and TNF alpha was al most completely abrogated in the microgravity cultures, suggesting that the IL-2 signaling pathways leading to various IL-2-mediated effects are diffe rentially regulated under bioreactor culture conditions. (C) 1999 Elsevier Science B.V. All rights reserved.