Abstract
The mode of action of cortisone as an antipyretic has been studied in rabbits challenged with intravenous injections of bacterial pyrogens. The fever induced by pyromen or dextran was found to be markedly suppressed when cortisone was administered in liberal amounts (25 mg. twice daily) for 3 days prior to the challenge. Although the cortisone effectively blocked the febrile response to both pyrogens, it failed to influence the transient but marked leucopenia which characteristically precedes the onset of fever. The antipyretic action of the drug also was shown to bear no relation to the activity of the serum factor recently demonstrated by Farr, Grant, and others to be involved in the production of pyrogen-induced fever. In preliminary experiments with typhoid vaccine as the inciting pyrogen, the presence of serum factor activity in normal blood and its absence in the blood of pyrogen-tolerant rabbits was confirmed. Subsequently the blood of rabbits treated with antipyretically effective doses of cortisone was shown to contain just as much serum factor activity as that of normal rabbits. In addition, previous incubation of the pyrogen with serum factor failed to influence the antipyretic effect of the drug. It is concluded from these findings that in suppressing pyrogen fever, cortisone acts neither upon the leucopenic reaction nor upon the fever-accelerating factor of the serum. By exclusion it would appear that the drug must influence some later stage of the fever-producing process. The mechanisms involved in the later stages of the response to exogenous pyrogen remain undefined, and the need for determining whether they are related to the prefebrile leucopenia is emphasized.
Full Text
The Full Text of this article is available as a PDF (747.6 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BENNETT I. L., Jr A study of the relationship between the fever caused by bacterial pyrogens and the fever accompanying acute infections. J Exp Med. 1948 Sep 1;88(3):267–278. doi: 10.1084/jem.88.3.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BENNETT I. L., Jr A study of the relationship between the fevers caused by bacterial pyrogens and by the intravenous injection of the sterile exudates of acute inflammation. J Exp Med. 1948 Sep 1;88(3):279–284. doi: 10.1084/jem.88.3.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BENNETT I. L., Jr, BEESON P. B. Studies on the pathogenesis of fever. I. The effect of injection of extracts and suspensions of uninfected rabbit tissues upon the body temperature of normal rabbits. J Exp Med. 1953 Nov;98(5):477–492. doi: 10.1084/jem.98.5.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BENNETT I. L., Jr, BEESON P. B. Studies on the pathogenesis of fever. II. Characterization of fever-producing substances from polymorphonuclear leukocytes and from the fluid of sterile exudates. J Exp Med. 1953 Nov;98(5):493–508. doi: 10.1084/jem.98.5.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BENNETT I. L., Jr, BEESON P. B. The effect of cortisone upon reactions of rabbits to bacterial endotoxins with particular reference to acquired resistance. Bull Johns Hopkins Hosp. 1953 Nov;93(5):290–308. [PubMed] [Google Scholar]
- BENNETT I. L., Jr, BEESON P. B. The properties and biologic effects of bacterial pyrogens. Medicine (Baltimore) 1950 Dec;29(4):365–400. doi: 10.1097/00005792-195012000-00003. [DOI] [PubMed] [Google Scholar]
- BENNETT I. L., Jr Production of fever and the Shwartzman phenomenon by native dextran. Proc Soc Exp Biol Med. 1952 Oct;81(1):266–268. doi: 10.3181/00379727-81-19843. [DOI] [PubMed] [Google Scholar]
- BERTHRONG M., CLUFF L. E. Studies of the effect of bacterial endotoxins on rabbit leucocytes. I. Effect of intravenous injection of the substances with and without induction of the local Shwartzman reaction. J Exp Med. 1953 Oct;98(4):331–348. doi: 10.1084/jem.98.4.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
- CHAMBERS W. W., KOENIG H. Site of action in the central nervous system of a bacterial pyrogen. Am J Physiol. 1949 Nov;159(2):209–216. doi: 10.1152/ajplegacy.1949.159.2.209. [DOI] [PubMed] [Google Scholar]
- DOUGHERTY T. F., SCHNEEBELI G. L. Role of cortisone in regulation of inflammation. Proc Soc Exp Biol Med. 1950 Dec;75(3):854–859. doi: 10.3181/00379727-75-18368. [DOI] [PubMed] [Google Scholar]
- DUFFY B. J., Jr, MORGAN H. R. ACTH and cortisone aggravation or suppression of the febrile response of rabbits to bacterial endotoxin. Proc Soc Exp Biol Med. 1951 Dec;78(3):687–689. doi: 10.3181/00379727-78-19182. [DOI] [PubMed] [Google Scholar]
- ESSEX H. E., GRANA A. Behavior of the leukocytes of the rabbit during periods of transient leukopenia variously induced. Am J Physiol. 1949 Sep;158(3):396–400. doi: 10.1152/ajplegacy.1949.158.3.396. [DOI] [PubMed] [Google Scholar]
- FARR R. S., CLARK S. L., Jr, PROFFITT J. E., CAMPBELL D. H. Some humoral aspects of the development of tolerance to bacterial pyrogens in rabbits. Am J Physiol. 1954 May;177(2):269–278. doi: 10.1152/ajplegacy.1954.177.2.269. [DOI] [PubMed] [Google Scholar]
- FARR R. S., LeQUIRE V. S. Leukocytic and pyrogenic effects of typhoid vaccine and augmentation by homologous plasma. Proc Soc Exp Biol Med. 1950 Dec;75(3):661–666. doi: 10.3181/00379727-75-18298. [DOI] [PubMed] [Google Scholar]
- Favorite G. O., Morgan H. R. EFFECTS PRODUCED BY THE INTRAVENOUS INJECTION IN MAN OF A TOXIC ANTIGENIC MATERIAL DERIVED FROM EBERTHELLA TYPHOSA: CLINICAL, HEMATOLOGICAL, CHEMICAL AND SEROLOGICAL STUDIES. J Clin Invest. 1942 Sep;21(5):589–599. doi: 10.1172/JCI101337. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GERMUTH F. G., Jr, OTTINGER B., OYAMA J. The influence of cortisone on the evolution of acute infection and the development of immunity. Bull Johns Hopkins Hosp. 1952 Jul;91(1):22–47. [PubMed] [Google Scholar]
- GLASER R. J., BERRY J. W., LOEB L. H., WOOD W. B., Jr The effect of cortisone in streptococcal lymphadenitis and pneumonia. J Lab Clin Med. 1951 Sep;38(3):363–373. [PubMed] [Google Scholar]
- GRANT R. Emotional hypothermia in rabbits. Am J Physiol. 1950 Feb;160(2):285–290. doi: 10.1152/ajplegacy.1950.160.2.285. [DOI] [PubMed] [Google Scholar]
- GRANT R. Nature of pyrogen fever; effect of environmental temperature on response to typhoid-paratyphoid vaccine. Am J Physiol. 1949 Dec;159(3):511–524. doi: 10.1152/ajplegacy.1949.159.3.511. [DOI] [PubMed] [Google Scholar]
- GRANT R. Refractorines to pyrogens, effects of incubation of pyrogen with plasma from normal and refractory donors on the responses of refractory recipients. Am J Physiol. 1953 May;173(2):246–252. doi: 10.1152/ajplegacy.1953.173.2.246. [DOI] [PubMed] [Google Scholar]
- GRANT R., WHALEN W. J. Latency of pyrogen fever; appearance of a fast-acting pyrogen in the blood of febrile animals and in plasma incubated with bacterial pyrogen. Am J Physiol. 1953 Apr;173(1):47–54. doi: 10.1152/ajplegacy.1953.173.1.47. [DOI] [PubMed] [Google Scholar]
- KASS E. H., FINLAND M. Effect of ACTH on induced fever. N Engl J Med. 1950 Nov 2;243(18):693–695. doi: 10.1056/NEJM195011022431803. [DOI] [PubMed] [Google Scholar]
- LEUSEN I. R., ESSEX H. E. Leukopenia and changes in differential leucocyte counts produced in rabbits by dextran and acacia. Am J Physiol. 1953 Jan;172(1):231–236. doi: 10.1152/ajplegacy.1952.172.1.231. [DOI] [PubMed] [Google Scholar]
- LeQUIRE V. S. The augmentation of the thermogenic effects of pyrogens by homologous plasma in rabbits. J Infect Dis. 1951 Mar-Apr;88(2):194–206. doi: 10.1093/infdis/88.2.194. [DOI] [PubMed] [Google Scholar]
- MOGABGAB W. J., THOMAS L. The effects of cortisone on bacterial infection; group A hemolytic streptococcal infection in rabbits. J Lab Clin Med. 1952 Feb;39(2):271–289. [PubMed] [Google Scholar]
- RECANT L., OTT W. H., FISCHEL E. E. The antipyretic effect of cortisone. Proc Soc Exp Biol Med. 1950 Oct;75(1):264–266. doi: 10.3181/00379727-75-18166. [DOI] [PubMed] [Google Scholar]
- REINER M. Effect of cortisone and adrenocorticotropin therapy on serum proteins in disseminated lupus erythematous. Proc Soc Exp Biol Med. 1950 Jul;74(3):529–531. doi: 10.3181/00379727-74-17962. [DOI] [PubMed] [Google Scholar]
- RICH A. R., BERTHRONG M., BENNETT I. L., Jr The effect of cortisone upon the experimental cardiovascular and renal lesions produced by anaphylactic hypersensitivity. Bull Johns Hopkins Hosp. 1950 Dec;87(6):549–567. [PubMed] [Google Scholar]
- VAUGHAN J. H., BAYLES T. B., FAVOUR C. B. Effect of 17-hydroxy-11-dehydrocorticosterone and adrenocorticotropic hormone upon plasma gamma globulin, fibrinogen, and erythrocyte sedimentation rate. Proc Soc Exp Biol Med. 1951 Feb;76(2):274–277. doi: 10.3181/00379727-76-18460. [DOI] [PubMed] [Google Scholar]
- WOODS A. C., WOOD R. M. The action of ACTH and cortisone on experimental ocular inflammation. Bull Johns Hopkins Hosp. 1950 Nov;87(5):482–504. [PubMed] [Google Scholar]
- WOOD W. B., Jr, SMITH M. R., PERRY W. D., BERRY J. W. Studies on the cellular immunology of acute bacteremia. I. Intravascular leucocytic reaction and surface phagocytosis. J Exp Med. 1951 Dec 1;94(6):521–534. doi: 10.1084/jem.94.6.521. [DOI] [PMC free article] [PubMed] [Google Scholar]