Edwin S. Miller

Inhibition of murine splenic T lymphocyte proliferation by 2-deoxy-D-glucose-induced metabolic stress

Female Swiss-Webster mice were injected with the glucose analogue 2-deoxy-D-glucose (2-DG), which when administered to rodents induces acute periods of metabolic stress. A single or multiple injections of 2-DG invoked a stress response, as evidenced by increases in serum corticosterone levels. The influence of this metabolic stressor on the blastogenic potential of splenic T lymphocytes was then examined. It was found that one, two, or three injections of 2-DG resulted in depressed T cell proliferative responses, with an attenuation of the effect occurring by the fifth injection. The 2-DG-induced inhibition of T cell proliferation was not attributable to 2-DG-induced cytolysis, as in vitro incubation of naive T cells with varying concentrations of 2-DG did not result in a reduction in cell number or viability, and flow cytometric analysis demonstrated that percentages of CD3, CD4, and CD8 splenic T cells were not altered as a result of 2-DG-induced stress. Incubating naive T cells in varying concentrations of 2-DG resulted in a dose-dependent inhibition of T cell blastogenic potential. Following in vivo exposure to 2-DG, T cell proliferation did not return to normal levels until 3 days after the cessation of 2-DG injections. Administering the beta-adrenergic receptor antagonist propranolol did not reverse the inhibited lymphoproliferation in 2-DG-treated mice. The inhibition in T cell proliferation was not observed, however, in mice that had been adrenalectomized or hypophysectomized and injected with 2-DG.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of antiorthostatic suspension on resistance to murine Listeria monocytogenes infection.

The present study was designed to evaluate the influence of antiorthostatic suspension, a ground‐based modeling system employed to simulate certain aspects of weightlessness that occur during space flight, on the capacity of mice to resist infection with the facultative intracellular bacterial pathogen Listeria monocytogenes. Female BDF1 mice were suspended by the tail in the orthostatic or antiorthostatic position and were infected with a sublethal dose of virulent L. monocytogenes at various times during the suspension. It was found that suspension did not influence the kinetics of bacterial growth in vivo if the infection was started concurrently with the suspension. However, mice that were antiorthostatically suspended 2, 4, or 7 days before the onset of infection exhibited an enhanced capacity to eliminate the challenge infection. Suspending mice on day 2 of the infection did not alter the kinetics of bacterial growth. Finally, the enhancement of resistance to the primary Listeria infection was accompanied by failure of the mice to generate long‐term protective immunological memory to the challenge organism. Collectively, these results indicate that the stress of antiorthostatic suspension can influence the capacity of mice to resist bacterial infection. J. Leukoc. Biol. 55: 371–378; 1994.

The role of cytokines in immune changes induced by spaceflight.

It has become apparent that spaceflight alters many immune responses. Among the regulatory components of the immune response that have been shown to be affected by spaceflight is the cytokine network. Spaceflight, as well as model systems of spaceflight, have been shown to affect the production and action of various cytokines including interferons, interleukins, colony stimulating factors, and tumor necrosis factors. These changes have been shown not to involve a general shutdown of the cytokine network but, rather, to involve selective alterations of specific cytokine functions by spaceflight. The full breadth of changes in cytokines in‐ duced by spaceflight, as well as mechanisms, duration, adaptation, reversibility, and significance to resistance to infection and neoplastic diseases, remains to be established.

Influence of suspension on the expression of protective immunological memory to murine Listeria monocytogenes infection.

Female BDF1 mice were immunized with virulent Listeria monocytogenes, which resulted in the generation of a long‐lived state of protective immunological memory for this facultative intracellular bacterial pathogen. The influence of antiorthostatic suspension, a ground‐based model employed to simulate certain aspects of weightlessness that occur during spaceflight, on the capacity of these mice to express memory immunity was evaluated. Memory‐immune mice were suspended by the tail in the orthostatic or antiorthostatic position and were reinfected with a lethal dose of virulent L. monocyto‐ genes. It was found that suspension did not influence the kinetics of bacterial growth in vivo when the rechallenge infection was started concurrently with the suspension. However, mice that were reinfected on day 2 or 4 of the suspension exhibited an enhanced capacity to eliminate the infection. Attenuation of this enhancing effect was observed when mice were infected on day 7 of the suspension. These results indicate that the stress of antiorthostatic suspension can influence the capacity of the murine host to express protective immunological memory to pathogenic bacteria.