Comparative Effects of Corticosteroids on Host Resistance to Infection in Relation to Chemical Structure

Abstract

As reported in a preceding paper (1), injections of hydrocortisone acetate into mice harboring latent corynebacteria (acquired either naturally or experimentally) evoke progressive and fatal corynebacterial pseudotubercutosis. That host resistance to a variety of infectious agents can be decreased by administration of corticoids has been repeatedly documented with regard to both experimental infections and activation of latent diseases (2-7). The early decrease of host resistance following corticoid injection is usually attributed to the suppression of the inflammatory process. In investigating the action of corticoids on phagocytic cells, we have had an opportunity to test the effect of 6a-methylprednisolone, 21 sodium hemisuccinate in vivo and in vitro. Despite the higher antiinflammatory activity of this compound as compared with hydrocortisone acetate, it was surprising that latent corynebacterial infection of mice was not provoked to active disease after injection of 6a-methylprednisolone, 21 sodium hemisuccinate as happened after injection of hydrocortisone acetate.The present report deals with this preliminary observation. It is shown, furthermore, that according to differences in the chemical structure of the steroids, different effects were observed with respect to host resistance even at the cellular level. These differences showed no correlation with the antiinflammatory properties of the drugs. Materials and MethodsM/~e.--The strains of mice and the sources from which they were obtained were the same as described in an earlier report (1) except for the NCS mice which came from the Pasteur Institute colony and were maintained as reported previously (1,8). Mice 4-6 wk of age were used for all experiments.

Cytoenzymology and ³H-Thymidine Uptake of Retro-Ocular. Connective Tissue Cultures in Experimental Endocrino-Exophthalmos

“…Our data concerning a decreased number of fibroblasts under the influence of cortisol confirm the observations of Bush [1956], Berliner and Ruhman [1966] and Fauve and Pierre Chase [1967] about the inhibition exerted by cortisol on fibroblast proliferation, thus explaining its anti inflammatory activity.…”

Biochemical actions of glucocorticoids on macrophages in culture. Specific inhibition of elastase, collagenase, and plasminogen activator secretion and effects on other metabolic functions.

“…Cells were grown on plates coated with ~SI-labeled fibrin, and the release of labeled peptides was monitored (171. Plasminogen activator was also measured in conditioned medium and cell lysates by the fibrin plate assay (17), by direct observation of conversion of l~SI-plasminogen to plasmin heavy and light chains (9), and by singlecell assays (13). 1 U of plasminogen activator solubilized 5% of the available ~I-fibrin/h in the presence of plasminogen (~1 tLg/h at 37°C ~.…”

Influence of Steroid Structure in Relation to Liver Metabolism during Endotoxin Lethality in Mice

“…All steroids that protected mice against endotoxin lethality (ta ble I) also increased glycogen levels (table 11). This gluconeogenic effect defines the glucocorticoid nature of a steroid molecule and appears intimately associated with the anti-inflammatory influence exerted by these molecules; however, 9-a-fluorohydrocortisone appears to possess primarily the glucocorticoid potential [6], Although the causal role of liver glycogen levels in determining the outcome of endotoxicosis has previously been challenged [2], these results are collectively in favor of the idea that inductive processes, leading to gluconeogenesis, are perhaps of importance in this regard. Data with liver TT establish clearly that such inductive processes were intact in all cases, due either to endogenous hormone release, or under the influence of exogenous steroid, or a com bination of both.…”