Histamine release inhibition in anti-inflammatory mechanism.

Rats were depleted of skin histamine by more than 80 % by intraperitoneal injections of sinomenine with daily increasing doses for 6 days. In these rats, egg-white edema induced in the hind paws was inhibited by 68 % of control. The weight of the wall of granuloma pouch made by croton oil was also evidently smaller in the rat treated similarly with sinomenine than that of control. This suggests an important role of histamine participating in the inflammation. It has been observed that a variety of non-steroidal anti-inflammatory drugs inhibited both degranulation and histamine release induced by compound 48/80 of mast cells isolated from rat peritoneal fluid. The degranulation inhibiting actions of anti-inflammatory drugs were markedly decreased in the presence of glucose as in cases of dinitrophenol, dicumarol and warfarin which are known uncouplers of oxidative phosphorylation. Also, prevention of edema provoked by anti-rat serum is roughly correlated to a potency of degranulation inhibiting effect of anti-inflammatory agents. These observations suggest that there is a common mechanism between these two phenomena, and the prevention of mast cell degranulation by the anti-inflammatory agents is, at least, partially due to their uncoupling effects. A working hypothesis explaining the process of edema formation at the inflammatory site has. been made based on the data of the present experiment and other ob3ervations: a leakage of plasma into the tissue space from the gap between two adjacent endothelial cells which are contracted by released histamine may activate a kinin-forming system in the plasma, and kinin(s) may further aggravate a leakage. The mechanism of action of anti-inflammatory agents, which interfere with the histamine effect in inflammation, should be understood in twofold: one is prevention of histamine release from the tissue, mainly by inhibiting mast-cell degranulation, and the other is prevention of the contraction of endothial cells by their uncoupling activities. ∗PMID: 4195455 [PubMed indexed for MEDLINE] Copyright c ©OKAYAMA UNIVERSITY MEDICAL SCHOOL Acta Med. Okayama 24, 113-129 (1970) HISTAMINE RELEASE INHIBITION IN ANTIINFLAMMATORY MECHANISM Hidemasa YAMASAKI, Kenji TASAKA, Kiyomi SAEKI and Shozo IRINO* Department of Pharmacology, Okayama University Medical School, Okayama, Japan Received for publication, December 15, 1969. Inflammation is a complex process involving many biochemical changes with the participation of several mediators. Since a number of factors should be considered, it is not easy to elucidate the role of a single mediator in the development of inflammation. Although it has been suggested that histamine plays an important role in inflammation, it is not possible to explain the whole set of events only by histamine action. In recent years, much attention has been turned to the other factors participating in the inflammation, such as serotonin (l) and bradykinin (2, 3). However, the degree of participation of each mediator is not the same regarding the etiology of inflammation and also varies with the species of animals (4). It has been mentioned that the common feature in various types of experimental inflammation is in delayed, prolonged permeability response, and histamine acts only in immediate, transient response. This immediate response of histamine can be seen both in rabbits and guinea pigs but not in rats (5). The present report concerns the experiments performed by using the rat to see the degree of histamine participation in experimental inflammation.