Antigen exposure is a strong stimulator of lymphocytes that triggers a variety of events including formation of cytokines such as interferon (IFN)-gamma (Cantrell, 1996), the defense against pathogen is impaired at high ambient osmolarity such as in the hyperosmolar renal medulla. Moreover, the immune response was reported to be impaired in diabetes Mellitus, which typically leads to increase of extracellular osmolarity,It cannot be excluded that "hyperglycemic memory" confounds the relationship between cell function and concomitant blood glucose concentration, i.e., hyperglycemia-induced changes in gene expression and biological reactions such as advanced glycation-end products in long-lived macromolecules may not be reversed when glycemia returns to normal, so that poor control is progressively "imprinted" on the cells , resulting in impairment of cellular immune activity.

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