Studies on the Dynamics of Biogenic Amines in Inflammatory Reactions

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Histamine is formed by histidine decarboxylase (HDC). Ornithine decarboxylase (ODC) is a rate-limiting enzyme in polyamine synthesis. The author had clarified the followings before the term of this grant-in-aid: (1) The injections of some kinds of inflammatory agents into mice induce HDC and ODC activities reaching peaks within 3 to 5 h in the tissues such as liver, lung, spleen and bone marrow. In the liver, serotonin is also accumulated. (2) Macrophages may participate in the induction of these responses. (3) P388Dl cells, a macrophage cell line, produce the factors capable of inducing all these responses. The molecular weight and isoelectric points of the factors are identical with those of interleukin-1 (IL-1), an important immuno-regulator. (4) Pharmacological suties suggest that the accumulation of 5HT in the liver may become a cause producing hypoglycaemia and hepatitis.During the term of the grant-in-aid, the followings were clarified: (5) IL-1 and TNF (tumor necrosis factor), … More products of macrophages, stimulate or suppress the growth of some types of tumor cells. These effects correlate to the expression or suppression of ODC activity in the cells. (6) Recombinant human IL-1 and TNF also induce all the responses as the inflammatory agents did. In addition, the combination of IL-1 and TNF enhanced these responses. These results confirms the observations in (3) and indicate that IL-1 and/or TNF can be regulators of these responses. (7) The accumulation of 5ht in the liver is due to the modilization of 5HT from other sites. Platelets may be involved in this mechanism.Conclusion: The mechainisms of the dynamics of the biogenic amines described above intimately correlate to the regulation of inflammatory or immune responses. The present and fufure fruits of this project will provide new clues for understanding inflammation of immune responses.One of two papers concerning (6) is in press and the other is in preparation. Further experiments are necessary for the publication of (7). The research on (5) was collaborated with National Cancer Institute of USA (Frederick, MD). Less