Pergamon Adv. SpaceRes. Vol. 14, No. 8, pp. (8)5-(8)9, 1994 Copyright@ 1994COSPAR Printedin Great Britain.All fights reserved. 0273-1177/94 $6.00 + 0.00 PRODUCTION AND ACTION OF CYTOKINES IN SPACE Stephen K. Chapes,* Dennis R. Morrison,** James A. Guikema,* Marian L. Lewis*** and Brian S. Spooner* * Division of Biology, Kansas State University, Manhattan, KS 66506, U.S.A. ** NASA-Johnson Space Center, Houston, TX 77058, U.S.A. *** Department of Biological Science, University of Alabama-HuntsviUe, AL 35899, U.S.A. ABSTRACI' B6MP102 cells, a continuously cultured murine bone marrow macrophage cell fine, were tested for secretion of tumor necrosis factor-a and Interleukin-1 during space flight. We found that B6MP102 cells secreted more tumor necrosis faetor-a and interleukin-1 when stimulated in space with fipopolysaccharide than controls similarly stimulated on earth. This compared to increased secretion of interferon-beta and -gamma by lymphocytes that was measured on the same shuttle flights. Although space flight enhanced B6MP102 secretion of tumor necrosis factor- a, an experiment on a subsequent space flight (STS-50) found that cellular cytotoxicity, mediated by tumor necrosis factor-a, was inhibited. INTRODUCTION Space flight has complex effects on individuals that occur at several levels. At one level, space flight and/or microgravity directly affect individual cells by interfering or enhancing cellular processes. At a second level, space flight and/or microgravity cause organismic or physiological changes that indirectly affect cells and/or organ systems. Therefore, it is important to understand and discriminate between changes at both levels. The immune response exemplifies cellular responses inducing systemic or whole organismic changes and make it an appropriate subject for study at both cellular and organismic levels. Host survival is dependent upon the maintenance of the immune system and its coordinated cellular components and cytokines. An interruption in one cellular component can hav~ catastrophic consequences. This is exemplified by acquired immune deficiency syndrome; the loss of CD4 "~ T cells leads to immunmuppression and death. NASA's long term plans for interplanetary travel are dependent upon the vigor and health of the astronaut crews. Became the immune system is dependent upon cytokines, it is important to determine if space flight affects their production or activity. To this end, we investigated the ability of a bone marrow-derived maerophage cell, B6MP102, to secrete cytokines. We compared B6MP102 secretion simultaneously with lymphocyte secretion of interferon. In addition, we determined whether space flight would affect the function of one cytokine, tumor necrmls factor-a O'NF). METHODOLOGY Cells The bone marrow-derived macrophage cell line, B6MP102, has been described previously/1/. The cells were grown in tissue culture dishes in preparation for shuttle flight/2/. Briefly, cells were dispersed wi~h trypsin plus EDTA, washed, counted and incubated on Cytodex 3 microcarrier beads. Between 2 and 5 x 10 U B6MP102 cells were incubated with 0.5 ml of a pelleted 2% Cytodex 3 bead solution for Space Transportation System (STS) flights 37 and 43. After attachment, beads-B6MP102 were washed and resuspended in HEPES-containing medium. 2 ml aliquots were aseptically dispensed into 5-ml syringes containing 10-~m filters and were shipped to Kennedy Space Center/2/. The B6MP102 cells were activated using 5-ml syringes mounted to bioprocessing modules (BPMs)/2,3/. The BPMs allowed injection of medium, with or without fipopolysaccharide (LPS) from one 5-ml syringe into the syringe containing the cells. After the incubation was completed, cell-free supernatant was injected into a third syringe where it was stored for return to earth for analysis. (8)5