Plasma Kinins and Cortisol: A Possible Explanation of the Anti-Inflammatory Action of Cortisol

Abstract

Kinins are naturally occurring vasoactive polypeptides thought to be mediators of acute inflammatory responses. Kinins are released from a plasma protein substrate by glass-activated plasma enzymes (kallikreins) or by isolated intact granulocytes. Cortisol in concentrations of 2.5 x 10(-6) to 2.5 x 10(-5)M prevented the release of active kinin from substrate by granulocytes or contact with glass. Deoxycorticosterone, progesterone, and etiocholanolone in comparable concentrations were significantly less effective in preventing kinin release. Plasma obtained from patients receiving prednisone released no kinin after activation by glass and less kinin than control plasma when exposed to granulocytes. Cortisol also partially inhibited the release of kinin by purified urinary kallikrein. Certain adrenocorticosteroids may exert their anti-inflammatory effect by inhibiting the release of plasma kinins. Steroids may act in part by preventing interaction between the activated kallikrein and its substrate.

Effects of Steroid Hormones on Human Polymorphonuclear Leukocyte Lysosomes

“…But direct membrane interaction by these compounds and resulting stabilization need not be invoked to explain their antiphlogistic actions. Corticosteroids have a wide range of biological activities that could account for their suppressive effects on inflammation (30)(31)(32)(33)(34). Interference with glucose transport (33) and inhibition of ATP generation (34), or suppression of NADH oxidase activity (5) are several actions that could lead to depressed cell function.…”

The release of a bradykinin‐like pulmonary vasodilator substance in foetal and new‐born lambs

“…The presence of some component of the buffy coat appears indispensable to rapid formation of kinin activity in foetal blood. There are several indications that this is the polymorphonuclear leucocyte fraction (Greenbaum, Freer & Kim, 1966;Cline & Melmon, 1966;Zachariae, Malmquist & Oates, 1966;Greenbaum & Kim, 1967).…”

PMN‐kinin and kinin metabolizing enzymes in normal and malignant leucocytes

“…Since the substrates used were purified, an additional complication in extrapolating to the in vivo situation would be the influence of other blood components on the activity of the kinin-forming enzymes. Nevertheless, the presence at inflammatory sites of large numbers of macrophages and other leucocytes such as PMN cells containing kininforming enzymes of activators of kinin-forming enzymes (Cline & Melmon, 1966) The inability of agents which are known to inhibit plasma kininases such as hydroxyquinoline, argininyl-phenylalanine, etc., to inhiibit the kininases of the types of leucocytes tested indicates that these kininases differ from tihe plasma kininases. It should be pointed out that in many laboratories hydroxyquinoline and other chelating agents are used to inhibit kininase activity when studying kinin formation.…”

“…Indeed, the role of plasma kallikrein in kinin formation in various phases of inflammation may be questioned by the fact that plasma kallikrein inhibitors such as Trasylol do not have proven effectiveness in the treatment of inflammatory disorders. In addition, the claim (Cline & Melmon, 1966) that steroids exert their anti-inflammatory activity by preventing the activation of plasma kallikrein has been questioned (Eisen, Greenbaum & Lewis, 1968). On the other hand, it has been shown that tissues such as spleen and liver contain kinin-forming and kinin-destroying enzymes which differ from their plasma counterparts in terms of their properties .…”