Abstract
In a comparative study concerning the effect of corticosteroids on host resistance to infections, five compounds were found to decrease host resistance, while three did not have this property, although all eight compounds were highly antiinflammatory. The compounds capable of decreasing host resistance were (I) hydrocortisone acetate; (III) 9α-fluoro, 16α-methylprednisolone acetate; (IV) 9α-fluoro, 16α-hydroxyprednisolone; (V) 9α-fluoro, 16α-hydroxyprednisolone, 16α–17α-acetonide; and (VII) 9α-fluoro, 16α-hydroxypredmsolone, 16α-, 17α-acetonide, 21 disodium phosphate. Following a single injection of 10 mg of any of these compounds, latent corynebacterial infection was provoked into active pseudotuberculosis. Also, mice injected with these corticosteroids were more susceptible to infection with Corynebacterium kutscheri, Staphylococcus aureus, Klebsiella pneumoniae, or Listeria monocytogenes. These same corticosteroids inhibited the ability of mouse peritoneal macrophages to spread on glass surfaces. The three compounds incapable of decreasing host resistance, although highly antiinflammatory, were: (II) 6α-methylprednisolone, 21 sodium hemisuccinate: (VI) 9α-fluoro, 16α-hydroxyprednisolone, 16α-, 17α-acetonide, 21 hemisuccinate; and (VIII) 9α-fluoro, 16α-hydroxyprednisolone, 16, 21 dihemisuccinate. These three compounds were also unable to inhibit the spreading of macrophages on glass. The importance of succinate group bound to the corticosteroid molecule as hemisuccinate is emphasized since it is seen that the infection-provoking property can be dissociated from the antiinflammatory property. This finding may be of practical consequence in selecting a corticosteroid for treatment in disease, and also shows that one cannot use, indifferently, corticosteroids only on the basis of their common antiinflammatory property.
Full Text
The Full Text of this article is available as a PDF (752.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- ALLISON F., Jr, ADCOCK M. H. FAILURE OF PRETREATMENT WITH GLUCOCORTICOIDS TO MODIFY THE PHAGOCYTIC AND BACTERICIDAL CAPACITY OF HUMAN LEUKOCYTES FOR ENCAPSULATED TYPE I PNEUMOCOCCUS. J Bacteriol. 1965 May;89:1256–1261. doi: 10.1128/jb.89.5.1256-1261.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
- ANTOPOL W., GLAUBACH S., QUITTNER H. Experimental observations with massive doses of cortisone. Rheumatism. 1951 Jan;7(1):187–196. [PubMed] [Google Scholar]
- COHN Z. A. Determinants of infection in the peritoneal cavity. II. Factors influencing the fate of Staphylococcus aureus in the mouse. Yale J Biol Med. 1962 Aug;35:29–47. [PMC free article] [PubMed] [Google Scholar]
- FAUVE R. M., PIERCE-CHASE C. H., DUBOS R. CORYNEBACTERIAL PSEUDOTUBERCULOSIS IN MICE. II. ACTIVATION OF NATURAL AND EXPERIMENTAL LATENT INFECTIONS. J Exp Med. 1964 Aug 1;120:283–304. doi: 10.1084/jem.120.2.283. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FRENKEL J. K. Evaluation of infection-enhancing activity of modified corticoids. Proc Soc Exp Biol Med. 1960 Mar;103:552–555. doi: 10.3181/00379727-103-25593. [DOI] [PubMed] [Google Scholar]
- Fauve R. M., Bouanchaud D., Delaunay A. Résistance cellulaire à l'infection bactérienne. IV. Immunisation active et résistance des macrophages de souris NCS à la multiplication intracellulaire de Listeria monocytogenes, Corynebacterium kutscheri et Brucella melitensis. Ann Inst Pasteur (Paris) 1966 Mar;110(3 Suppl):106–117. [PubMed] [Google Scholar]
- Fauve R. M., Delaunay A. Etablissement d'une colonie pilote de souris N. C. S. Ann Inst Pasteur (Paris) 1966 Feb;110(2):283–290. [PubMed] [Google Scholar]
- GERMUTH F. G., Jr The role of adrenocortical steroids in infection, immunity and hypersensitivity. Pharmacol Rev. 1956 Mar;8(1):1–24. [PubMed] [Google Scholar]
- HIRSCH J. G., CHURCH A. B. Adrenal steroids and infection: the effect of cortisone administration on polymorphonuclear leukocytic functions and on serum opsonins and bactericidins. J Clin Invest. 1961 May;40:794–798. doi: 10.1172/JCI104312. [DOI] [PMC free article] [PubMed] [Google Scholar]
- KASS E. H. Hormones and host resistance to infection. Bacteriol Rev. 1960 Mar;24(1):177–185. doi: 10.1128/br.24.1.177-185.1960. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LERNER L. J., TURKHEIMER A. R., BIANCHI A., SINGER F. M., BORMAN A. COMPARISON OF ANTI-GRANULOMA, THYMOLYTIC AND GLUCOCORTICOID ACTIVITIES OF ANTI-INFLAMMATORY STEROIDS. Proc Soc Exp Biol Med. 1964 Jun;116:385–388. doi: 10.3181/00379727-116-29255. [DOI] [PubMed] [Google Scholar]
- LeMAISTRE C., TOMPSETT R. The emergence of pseudotuberculosis in rats given cortisone. J Exp Med. 1952 Apr;95(4):393–408. doi: 10.1084/jem.95.4.393. [DOI] [PMC free article] [PubMed] [Google Scholar]