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Norepinephrine is a stress hormone that enhances bacterial growth. We examined the effects of a small inoculum on the norepinephrine-induced growth of species previously reported to be unaffected by norepinephrine. The results indicated that a reduced inoculum density is essential for observing norepinephrineinduced effects. Additional studies using serum-free media suggested that transferrin plays a role in norepinephrine-induced growth.Determining the direct effect of catecholamines on the in vitro growth response of bacteria is one interdisciplinary approach that has been utilized to increase our understanding of the role that stress hormones play in the establishment and progression of infection in a host (21). Although a great deal of evidence suggests that stress-induced neurohormones play a critical role in the outcome of infections (1,3,4,5,7,21,31), the mechanisms by which these hormones act in the host remain unclear. Studies with human and animal models have indicated that increased levels of stress hormones, including norepinephrine (NE), as well as other catecholamines, alter the immune response and physiology of the host (2). High circulatory levels of these hormones are detected in individuals exposed to a variety of physically and/or mentally stressful situations, including trauma, space flight, and sepsis (13,29,31,32). The increases not only may alter the immune function but also may contribute to host morbidity and increased risk of infection (1,7,34). In the current study we reexamined the in vitro growth responses of a variety of bacterial species that were previously tested and reported not to be enhanced by the addition of NE (6,8).The conditions employed in this study include a minimally nutritive low-iron medium previously shown to maintain bacteriostasis (21), a low initial inoculum density of bacteria (10 CFU/ml) in order to capture the lag phase of the bacterial growth curve typically observed in a bacteriostatic medium (21,26), and a concentration of NE (0.0001 M) (14, 15, 26) which corresponds to target tissue levels and not mere plasma spillover (16,18,20). These rigorous conditions better represent in vivo milieus and also allow more suitable evaluation of a growth enhancement effect without the camouflage of rapid bacterial growth encountered when rich medium and large inocula are employed.Using a lower initial inoculum density (approximately 10 CFU/ml), each species tested exhibited NE-induced enhancement of in vitro growth compared to nontreated controls. Cultures of Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter cloacae, Shigella sonnei, and Staphylococcus aureus grown in the presence of NE had shortened lag times and exhibited significant increases in bacterial counts (CFU/ml) at 18 and 24 h (Fig. 1) compared to the control. Moreover, for all of the gram-negative pathogens there were other times when there were significant increases in growth (Fig. 1A to D). S. aureus growth was only moderately affected by NE treatment, and there were significant differences in g...

Experiments were carried out aboard COSMOS 2044 to determine the effects of spaceflight on immunologically important cell function and distribution. Control groups included vivarium, synchronous, and antiorthostatically suspended rats. In one experiment, rat bone marrow cells were examined in Moscow, for their response to recombinant murine granulocyte/monocyte colony-stimulating factor (GM-CSF). In another experiment, rat spleen and bone marrow cells were stained in Moscow with a variety of antibodies directed against cell surface antigenic markers. These cells were preserved and shipped to the United States for analysis on a flow cytometer. Bone marrow cells from flown and suspended rats showed a decreased response to granulocyte/monocyte colony-stimulating factor compared with bone marrow cells from control rats. Of the spleen cell subpopulations examined from flown rats, only those cells expressing markers for suppressor-cytotoxic T- and helper T-cells showed an increased percentage of stained cells. Bone marrow cells showed an increase in the percentage of cells expressing markers for helper T-cells in the myelogenous population and increased percentages of anti-asialo granulocyte/monocyte-1-bearing interleukin-2 receptor-bearing pan T- and helper T-cells in the lymphocytic population. Cell populations from rats suspended antiorthostatically did not follow the same pattern of distribution of leukocytes as cell populations for flown rats. The results from COSMOS 2044 are similar, but not identical, to earlier results from COSMOS 1887 and confirm that spaceflight can have profound effects on immune system components and activities.

Space flight conditions have a dramatic effect on a variety of physiologic functions of mammals, including muscle, bone, and neurovestibular function. Among the physiological functions that are affected when humans or animals are exposed to space flight conditions is the immune response. The focus of this review is on the function of the immune system in space flight conditions during actual space flights, as well as in models of space flight conditions on the earth. The experiments were carried out in tissue culture systems, in animal models, and in human subjects. The results indicate that space flight conditions alter cell-mediated immune responses, including lymphocyte proliferation and subset distribution, and cytokine production. The mechanism(s) of space flight-induced alterations in immune system function remain(s) to be established. It is likely, however, that multiple factors, including microgravity, stress, neuroendocrine factors, sleep disruption, and nutritional factors, are involved in altering certain functions of the immune system. Such alterations could lead to compromised defenses against infections and tumors.

Interferon (IFN), types beta and gamma, and IFN inducers polyinosinic-polycytidylic acid and lymphocytic choriomeningitis virus all stimulated the generation of blast-NK cells in mouse spleens. Blast-NK cells were characterized on the basis of size, 3H-thymidine uptake, and NK cell markers. These data indicate that in addition to augmenting NK cell-mediated lysis, IFN may regulate NK cell proliferation in vivo.

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It has been reported that spaceflight conditions alter the immune system and resistance to infection [Belay T, Aviles H, Vance M, Fountain K, and Sonnenfeld G. J Allergy Clin Immunol 170: 262-268, 2002; Hankins WR and Ziegelschmid JF. In: Biomedical Results of Apollo. Washington, DC: NASA, 1975, p. 43-81. (NASA Spec. Rep. SP-368)]. Ground-based models, including the hindlimb-unloading model, have become important tools for increasing understanding of how spaceflight conditions can influence physiology. The objective of the present study was to determine the effect of hindlimb unloading on the susceptibility of mice to Pseudomonas aeruginosa infection. Hindlimb-unloaded and control mice were subcutaneously infected with 1 LD50 of P. aeruginosa. Survival, bacterial organ load, and antibody and corticosterone levels were compared among the groups. Hindlimb unloading had detrimental effects for infected mice. Animals in the hindlimb-unloaded group, compared with controls, 1). showed significantly increased mortality and reduced time to death, 2). had increased levels of corticosterone, and 3). were much less able to clear bacteria from the organs. These results suggest that hindlimb unloading may induce the production of corticosterone, which may play a critical role in the modulation of the immune system leading to increased susceptibility to P. aeruginosa infection.