Dorothy K. Gauthier

Cytokine and hormone profiles in mice subjected to handling combined with rectal temperature measurement stress and handling only stress

Stress is known to either up or down regulate immunity. In this study, mice were subjected to handling combined with rectal temperature measurement (RTM) stress or handling only stress. We investigated whether there were any significant differences in the effect of handling combined with RTM and handling only on NK cell activity, serum cytokine (IL-1beta, IL-6, and TNF-alpha) and ACTH and beta-endorphin levels, and splenic cytokine (IL-1beta, IL-6, TNF-alpha, IFN-alpha, and IFN-beta) levels. Circulating cytokines and hormones and splenic cytokine mRNA levels were measured in individual mice. NK cell activity was significantly increased in both stress groups when compared to the control group. Handling combined with RTM produced significantly increased serum levels of IL-1beta, IL-6, and beta-endorphin. Serum IL-1beta, ACTH, and beta-endorphin were elevated significantly in the handling only group. Splenic TNFalpha mRNA in both of the stress groups and IL-6 mRNA in handling only group decreased significantly. Our observations are supported by existing literature demonstrating that various stressors have differential effects on immune functions and the neuroendocrine hormones and cytokines, which regulate them.

Effects of Rotational Stress of Different Duration on NK Cell Activity, Proinflammatory Cytokines, and POMC-Derived Peptides in Mice

Previous studies have shown that the same stressor, depending on intensity, controllability, or duration, can have different effects on the immune system. The purpose of this study was to determine the effect of 10- and 20-min rotation on natural killer (NK) cell activity and also to establish if changes in body temperature, proinflammatory cytokine (IL-1β, IL-6, and TNF-α) levels, and proopiomelanocortin (POMC)-derived peptide (ACTH and β-endorphin) levels parallel the changes in NK cell activity in mice. We found that 10-min rotation significantly increased NK cell activity as compared to both the control (home cage) group and the 20-min-rotation group, while NK cell activity in the 20-min group was not significantly changed compared to the control group. Both 10 and 20 min of rotational stress decreased body temperature and induced significant changes in the proinflammatory cytokine and POMC-derived peptide levels as compared to the control group. The pattern of proinflammatory cytokine expression was quite different between the 10- and 20-min rotation groups. All three proinflammatory cytokines were expressed sequentially (at 0 h after rotation TNF-α, at 6 h IL-1β and IL-6, and at 24 h IL-6) in the 10-min rotation group, while the 20-min rotation group had a small increase in IL-1β (6.7 ± 1.8 pg/ml) at 0 h and increased levels of IL-6 at 6 and 24 h. There was a dissociation of ACTH and β-endorphin expression in both groups resulting in significantly more β-endorphin (p < 0.05) in the 10-min group at 6 h and significantly more ACTH (p < 0.04) in the 20-min group at 6 h. IL-1β and β-endorphin have both been shown to have a direct stimulatory effect on NK cell activity. Therefore, we suspect that the significant increase in both IL-1β and β-endorphin at 6 h in the 10-min-rotation group may be involved in the increased NK cell activity observed at 24 h in the 10-min-rotation group.

Anti-HIV antibody testing: Procedures and precautions

Prudent use of screening tests for infection with human immunodeficiency virus (HIV) and interpretation of test results require an understanding of the bodys immune response to HIV infection, the serologic assays currently available, and the problems associated with false-positive and false-negative test results. The methodologies of the enzyme immunoassay (enzyme-linked immunosorbent assay [ELISA]) and the Western blot assay are presented, and efficacies of these tests are evaluated. Tests for the detection of anti-HIV antibodies that are, at this time, primarily restricted to research use but that show promise for adaptation to screening (such as the ELISA with recombinant antigen) also are discussed, as is the alternative of testing for HIV antigens or HIV-specific DNA. From a personal perspective, any test for HIV infection is accompanied by certain benefits and risks. These can be discussed with the patient in the framework of pretest and posttest counseling.

Immunotherapy of a murine T cell lymphoma localized to the brain.

Mouse YC8 T cell lymphoma was used as a model to determine whether an effective immunotherapy procedure could be devised for the treatment of lymphoma localized to the brain. Implantation of 5 × 104 YC8 cells into the left cerebral hemisphere induced rapid loss of the animals body weight. Severe loss of weight and early deaths were observed in the untreated control group. Although resistance can be conferred to the brain by immunization of naive BALB/c mice, adoptive chemoimmunotherapy procedures were surprisingly not effective in inducing remissions in animals with lymphoma confined to the brain. Even passive transfer of effector cells from immunized, tumor resistant donor animals combined with systemic IL-2 treatment did not impart resistance to recipients with brain tumors. However, regression of the intracranial tumor and apparent cures could be accomplished, when ex vivo cultured effector cells were transferred intravenously.

Trauma: The Acute Response

Moderate to severe trauma is followed by a local response, which involves changes in cell function and an inflammatory reaction, and a systemic response coordinated by the nervous and endocrine systems. Early post-trauma alterations in cells are due primarily to decreased oxygen supply and include 1) the shifting of electrolytes and water, either into or out of cells, and 2) the production or release of various local tissue factors. These tissue factors produce changes in blood flow, increased vascular permeability, and other local manifestations of inflammation. Trauma activates nervous and hormonal pathways which help to restore blood volume and maintain the function of essential organs. The effects of these responses on cellular oxygen consumption and body temperature are described. Examples of respiratory system involvement in response to trauma in the lungs or elsewhere are given. These include increased capillary permeability in the lungs, pulmonary emboli, and damage from smoke and heat inhalation.