Lymphocyte Cyclic Nucleotides and Cellular Immunity in Viral Hepatitis

Abstract

It has been known that contents of intra-cellular cyclic nucleotides, cyclic 3', 5'-adenosine monophosphate (cyclic AMP) and cyclic 3', 5,-guanosine monophosphate (cyclic GMP), in T-lymphocytes are closely related with cell-mediated immunity of the host since the first investigations by Lichtenstein & Margolis (1968). However, this problem has never been studied in human viral hepatitis. Therefore, we began the clinical and experimental studies on this problem. It is illustrated in this study that the intracellular cyclic-AMP content of T-lymphocyte in peripheral blood was enhanced by an addition of phytohemagglutinin (PHA) to lymphocyte culture medium. The increase-rate of lymphocytic cyclic-GMP content caused by the addition of similar mitogen was reduced in patients of chronic active hepatitis when compared with normal control. The relationship between the contents of intracellular (lymphocytes) cyclic AMP and serum levels of α₂-macroglobulin which is thought to be one component of serum inhibitors against the non-specific cell-mediated immunity in our previous data was investigated in this study, and these markers showed the parallel variation with each other in the patients of viral hepatitis. On the other hand, the high cyclic AMP content and low cyclic GMP increase-rate by an addition of mitogen to peripheral T-lymphocyte culture medium (as well as high serum α₂-macroglobulin levels) were seen in patients with chronic active hepatitis which meant a suppressed cellular immunity. In conclusion, a determination of cyclic nucleotides in T-lymphocytes is very useful to understand the involvement of them in cell-mediated immunity which is closely associated with chronicity of viral hepatitis.