One of the most compelling, yet challenging, aspects of immunology is to understand the mechanisms by which individual parts integrate into a functiona whole. Limited studies have addressed this imporissue. Corticosteroids, which are released during cold stress, hypothermia, or both, have a welldocumented immunosuppressive effect. when cold stress is applied to an animal, specific changes n the cellular components can be observed Sundaresan and colleagues' showed that when albino rats were subacutely stressed with cold water immersion, the total number of immune cells was initially expanded. Total white cell count was in creased, as were total numbers of eosinophils and basophils. Phagocytic and avidity indices were also increased in phagocytic cells. However, Cheng and showed that prolonged cold water colleagues stress actually has an immunosuppressive effect they reported a decreased number of thymocytes and splenocytes, as well as diminished blastogenesis of T cells and lowered activity of natural killer cells. Macrophages were found to be less responsive to interferon gamma, and because these antigenpresenting cells are crucial for initiating immune cascades, the impairment of macrophage function could be a significant cause of a dampened immune esponse. While the mice in the Cheng experiment were obviously also stressed by anxiety and exercise, these results have implications for many settings of human accidental hypothermia
Aarstad' reconfirmed the results of Cheng, in that an absolute value of cluster of differentiation 4+ (CD4+) cells, which are most commonly considered to be helper T cells, was affected by cold stress but not that of CD8+ cells, which are most commonly considered to be killer T cells. In the Aarstad experiments, the number of stressors per day, as as the duration of the trial, were varied and had an effect on the various populations of cells For example, mice stressed once a day actually showed an increase in the percentage of CD4+ cells, while the mice stressed twice a day showed a decrease
Current data suggest that the immune system is significantly impaired in hypothermic settings Some studies, however, indicate the contrary: that antibody-antigen interactions may actually be stronger at colder temperatures. Further, the optimal working temperature of complement is said to be 20°C to 25°C. However, as was previously reiterated, many of the cell-mediated responses and the microenvironmental conditions that are critical to an active immune response are made defective by cold. To emphasize what has been presented, two of the more important players for initiating an immune cascade, helper T lymphocytes and macrophages are specifically inhibited by cold
Finally, it is also important to consider the microvasculature changes to cold, both local and throughout the body. Viscosity of the blood increases with cold, due in part to the aggregation of red blood cells and the increased adhesion of white blood cells to the endothelium. Capillary occlusion is possible, leading to hypoxic damage. Endrich and colleagues report a result different from many others; namely, an observed increase in the permeability of the chilled vessels to macromolecules, leading to some leukocyte extravasation before the increased adherence of these cells. Overall, cold affects the immune response not only by inhibition of specific cells but also through blood cell and vascular changes, such as alterations in viscosity of the blood and permeability of the vessels
Acclimation may play a major role in attenuating a response to an acute cold stress. Kizaki and colleagues reported that in response to an acute cold stress, cold-acclimated mice exhibited a significant attenuation of the increases in serum cortico-sterone levels and the expression of the GC-receptor messenger RNA on peritoneal exudate cells. If one can extrapolate from these studies to humans, it is conceivable that humans who are acclimated to cold may be able to withstand a cold stress and minimize any major alterations in their immune response.