Leukocytes come into intimate contact with the venular endothelium as they extravasate from blood to the interstitium during inflammation. In exteriorized tissues, the number of leukocytes rolling along the vessel wall was markedly increased in adrenalectomized and metyrapone-treated animals, relative to sham-operated and normal animals. During the development of an acute, local inflammatory response, rollers were numerically decreased and a stronger adhesion of the cells to the en- dothelium, with a concomitant migration into tissues, was observed. Adhesion and migration were much more marked in adrenalectomized and metyrapone-treated animals than in controls, suggesting that secreted gluco- corticoids exert a suppressive effect on leukocyte-endo- thelial internctions. The increased number of rolling leu- kocytes in adrenalectomized and metyrapone-treated animals apparently resulted in more cells available to migrate into inflamed tissues. The effect appears to in- volve receptor occupancy and induction of gene expres- sion because normal animals receiving the steroid an- tagonist RU 38 486, actinomycin D, or cydoheximide behaved as adrenalectomized or metyrapone-treated animals. Administration to adrenalectomized animals of a monoclonal antibody to the membrane glycoprotein complex CD18 did not affect the number of rolling cells, but dramatically reduced the number of adherent or migrated leukocytes. It is suggested that secreted glucocorticoids, in addition to an effect on rolling be- havior of circulating leukocytes, might also modulate the activity of the glycoprotein complex CD18 on white blood cells. The ultimate consequence is a restrictive effect on cell emigration in inflammation. J. Leukoc. Biol. 57: 379-386; 1995.

Secreted glucocorticoids regulate leukocyte-endothelial interactions in inflammation. A direct vital microscopic study

We describe that an ongoing inflammatory response at one site (produced by complete Freund's adjuvant injection in the hindpaw) produces a negative feedback inhibition on plasma extravasation, produced by perfusion of the inflammatory mediator, bradykinin (160 nM), at a second site (the knee joint). This negative feedback process is abolished in rats that have been neonatally treated with capsaicin to deplete most of their unmyelinated primary afferent fibers, which suggests that this negative feedback process is mediated by activation of primary afferent fibers. Electrical stimulation of the hindpaw at intensities that excite C-fibers also inhibited bradykinin-induced plasma extravasation. Stimulation at intensities that only excite A-fibers had no effect on bradykinin-induced plasma extravasation. Platelet activating factor-induced plasma extravasation, which is not dependent on the innervation of the joint, was not inhibited by stimulation of C-fibers from the hindpaw. Acute surgical interruption of the lumbar sympathetic outflow to the hind limb (the paravertebral ganglia between L2 and L4) did not attenuate the depression of bradykinin-induced plasma extravasation produced by C-fiber stimulation. This indicates that the depression is not mediated by activity in the sympathetic outflow. Transection of the spinal cord, hypophysectomy, inhibition of corticosterone synthesis, and adrenalectomy (but not adrenal medullectomy) all prevented the inhibition of BK-induced plasma extravasation by electrical simulation, indicating that the negative feedback inhibition on plasma extravasation is dependent on an intact neuraxis and an intact hypothalamic-pituitary-adrenocortical axis. In summary, our data demonstrate a negative feedback inhibition of an inflammatory process, which is elicited by stimulation of C-fiber afferents.(ABSTRACT TRUNCATED AT 250 WORDS)

https://www.jneurosci.org/content/jneuro/15/6/4678.full.pdf

Negative Feedback Neuroendocrine Control of the Inflammatory Response in Rats

Carrageenin causes a reproducible inflammatory reaction and remains the standard irritant for examining acute inflammation and anti-inflammatory drugs. High doses of diazepam (10.0-20.0 mg/Kg) were shown to reduce the volume of acute inflammatory paw edema in rats as a response to carrageenin administration. The present experiment was undertaken to investigate the possible roles of peripheral-type benzodiazepine receptors (PBRs) and corticosterone on the anti-inflammatory effects of diazepam. Five experiments were conducted to assess the effects of a single dose (10.0 mg/Kg) of diazepam on carrageenin-induced paw edema (CIPE), pleurisy and increase in vascular permeability in rats. Results showed that: 1. diazepam or Ro5-4864 (a PBR agonist) treatment reduced CIPE values; 2. prior treatment with PK11195 (a non-benzodiazepine PBR antagonist) suppressed the effects of either diazepam or Ro5-4864 on CIPE; 3. diazepam reduced the volume of the pleural exudate in carrageenin-injected rats, as well as its leukocyte count; 4. diazepam treatment reduced the magnitude of the increase in vascular permeability caused by carrageenin; 5. adrenalectomy suppressed the effects of diazepam on CIPE; and 6. diazepam treatment increased the serum concentration of corticosterone. These results suggest a relevant role of PBR and corticosterone on diazepam-induced changes in inflammation. They are discussed in the light of a possible activation of mitochondrial PBRs within the adrenal gland cells by diazepam, thereby increasing the serum levels of corticosterone and thus reducing CIPE.

Reduction of acute inflammation in rats by diazepam: role of peripheral benzodiazepine receptors and corticosterone

Inflammation induced by inactivated Aeromonas hydrophila in Nile tilapia fed diets supplemented with Saccharomyces cerevisiae.

Almost any stage of inflammatory and immunological responses is affected by hormone actions This provides the basis for the suggestion that hormones act as modulators of the host reaction against trauma and infection Specific hormone receptors are detected in the reactive structures in inflamed areas and binding of hormone molecules to such receptors results in the generation of signals that influence cell functions relevant for the development of inflammatory responses Diversity of hormonal functions accounts for recognized pro- and anti-inflammatory effects exerted by these substances Most hormone systems are capable of influencing inflammatory events Insulin and glucocorticoids, however, exert direct regulatory effects at concentrations usually found in plasma Insulin is endowed with facilitatory actions on vascular reactivity to inflammatory mediators and inflammatory cell functions Increased concentrations of circulating glucocorticoids at the early stages of inflammation results in downregulation of inflammatory responses Oestrogens markedly reduce the response to injury in a variety of experimental models Glucagon and thyroid hormones exert indirect anti-inflammatory effects mediated by the activity of the adrenal cortex Accordingly, inflammation is not only merely a local response, but a hormone-controlled process

https://downloads.hindawi.com/journals/mi/1993/602891.pdf

F.R. Moraes

Papers

Endogenous corticosteroids and insulin in acute inflammation