1887

Chapter 16 : Effects of Cortisone and Adrenocorticotropic Hormone on Tuberculosis

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in
Zoomout

Effects of Cortisone and Adrenocorticotropic Hormone on Tuberculosis, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815684/9781555813734_Chap16-1.gif /docserver/preview/fulltext/10.1128/9781555815684/9781555813734_Chap16-2.gif

Abstract:

Pharmacological amounts of glucocorticoids are frequently given as therapy for a variety of allergic, autoimmune, and inflammatory conditions, such as asthma and rheumatoid arthritis. When such drugs are continued for long periods of time, latent tuberculosis may reactivate. In tuberculous rabbits infected with human-type tubercle bacilli, pharmacological amounts of glucocorticoids decreased cell-mediated immunity and delayed-type hypersensitivity. Macrophages were poorly activated, and tubercle bacilli grew to large numbers within these phagocytes. After glucocorticoid administration was stopped, the tuberculin sensitivity returned, and (because of the large numbers of bacilli) liquefaction, cavity formation, tuberculous bronchopneumonia, and hematogenous dissemination occurred in some of the rabbits. One of Lurie’s inbred rabbit strains was evidently deficient in glucocorticoid production. In these rabbits, the administration of physiological doses of adrenocorticotropic hormone increased their resistance to tuberculosis. This chapter would not be complete without mention of dehydroepiandrosterone (DHEA) and 3β,17β-androstenediol (AED). These corticosteroids counteract the adverse effects of glucocorticoids on tuberculosis. The adrenals of different animal species secrete different proportions of glucocorticoids: e.g., rabbits and rats have low ratios of 17- hydroxycorticosterone (hydrocortisone) to corticosterone, whereas monkeys and humans have high ratios. Five weeks after infection with human-type tubercle bacilli, Lurie’s resistant strain III rabbits apparently produced higher levels of both hormones than did his susceptible strain FC rabbits.

Citation: Dannenberg, Jr. A. 2006. Effects of Cortisone and Adrenocorticotropic Hormone on Tuberculosis, p 273-284. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch16
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of FIGURE 1
FIGURE 1

Lungs of control rabbit FC 2-46 (left) and cortisone-treated rabbit FC 2=1 (right) 5 weeks after the inhalation of aerosolized virulent human-type tubercle bacilli (H37Rv). The lungs are black, because shortly before the rabbits were euthanized, an intravenous injection of carbon particles (India ink) was made to assess the phagocytic abilities in the liver and spleen.

Note that (i) fewer grossly visible primary pulmonary tubercles are present in the corticosteroid-treated animal, (ii) their size is smaller, (iii) their caseous centers are whiter, and (iv) little perifocal inflammation exists around the caseous centers. Reproduced with permission from reference 6.

Citation: Dannenberg, Jr. A. 2006. Effects of Cortisone and Adrenocorticotropic Hormone on Tuberculosis, p 273-284. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2
FIGURE 2

A tissue section of a primary tubercle from the lungs of a cortisone-treated rabbit (A) and a control rabbit (B), 5 weeks after the inhalation of an aerosol of virulent human-type tubercle bacilli (H37Rv). These specimens were from the same experiment as that depicted in Fig. 1. (A) The tubercle of the cortisone-treated rabbit shows intra-alveolar plugs of necrotic macrophages containing very large numbers of tubercle bacilli. The alveolar walls are thin with little or no cell infiltration, because the glucocorticoids reduced the inflammatory response. (B) The tubercle of the control rabbit (which received no glucocorticoids) shows extensive perifocal inflammation and more mature (i.e., more homogeneous) caseation. Relatively few bacilli were present (not visible at this magnification). Reproduced with permission from reference 6.

Citation: Dannenberg, Jr. A. 2006. Effects of Cortisone and Adrenocorticotropic Hormone on Tuberculosis, p 273-284. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3
FIGURE 3

Size of BCG lesions and size of dermal tuberculin reactions in cortisone-treated and control rabbits at various times after the BCG lesions were produced. Cortisone treatment markedly reduced the size of both the BCG lesions and the tuberculin reactions, because there was less cell infiltration in each (see Fig. 4). Reproduced with permission from reference 11.

Citation: Dannenberg, Jr. A. 2006. Effects of Cortisone and Adrenocorticotropic Hormone on Tuberculosis, p 273-284. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4
FIGURE 4

Tissue sections of 12-day BCG lesions from a cortisone-treated rabbit (A) and a control rabbit (B) stained for β-galactosidase, our marker enzyme for macrophage activation (12–14). Near the necrotic center of the control lesion are large β-galactosidase-positive epithelioid cells (activated macrophages). Such mature epithelioid cells are almost absent in the lesion of the cortisone-treated rabbit (P = 0.001). Stained with 5-bromo-4-chloro-3-indolyl-β--galactoside, hematoxylin, and carbol-fuchsin.

Both photographs are at the same magnification (×155). When macrophages become activated, they greatly increase in size. Reproduced with permission from reference 11.

Citation: Dannenberg, Jr. A. 2006. Effects of Cortisone and Adrenocorticotropic Hormone on Tuberculosis, p 273-284. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 5
FIGURE 5

Tissue sections of 18-day BCG lesions from a cortisone-treated rabbit (A) and a control rabbit (B), showing the size of their necrotic liquefied centers. Note that cortisone treatment reduced the lesion size, the amount of cell infiltration, the amount of necrosis, and the β-galactosidase activity (recognized here by the dark-staining cells in the infiltrate). Stained with 5-bromo-4-chloro-3-indolyl-β--galactoside, hematoxylin, and carbol-fuchsin. Magnification, ×10. Reproduced with permission from reference 11.

The volumes of the necrotic centers illustrated were 16 mm3 in the cortisone-treated rabbit and 46 mm3 in the control rabbit. The average volume of these centers for the six cortisone-treated rabbits (in the 18-day BCG group of this experiment) was 5.0 ± 2.5 mm3, and that for the six control rabbits was 28 ± 7 mm3 (P = 0.01) (11).

Citation: Dannenberg, Jr. A. 2006. Effects of Cortisone and Adrenocorticotropic Hormone on Tuberculosis, p 273-284. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 6
FIGURE 6

Lungs of a control rabbit of the inbred susceptible Ca strain (Ca 5-23) (left) and a cortisone-treated rabbit of the same strain (Ca 4-7) (right). These rabbits had inhaled aerosols of virulent human-type tubercle bacilli (H37Rv) 11 weeks previously. The cortisone treatment was started 4 days before infection and continued for 6 weeks during infection. Five weeks after the cortisone treatment was stopped, the rabbit died of massive caseous pneumonia with liquefaction (shown on the right). It had both bronchial and hematogenous spread of the disease. At this time, the control rabbit (which had received diluent alone) had regressive pulmonary tubercles with evidence of healing (shown on the left).

These studies clearly demonstrate the dangers of pharmacological glucocorticoid therapy in tuberculous hosts, i.e., a marked decrease in the host’s ability to control bacillary growth and, after hormone withdrawal, an extensive delayed-type hypersensitivity reaction to accumulated bacillary products (see text).

Reproduced with permission from reference 2.

Citation: Dannenberg, Jr. A. 2006. Effects of Cortisone and Adrenocorticotropic Hormone on Tuberculosis, p 273-284. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 7
FIGURE 7

Lungs of control rabbits of the inbred resistant strains (IIIFIII 1-16 and III IIIC 1-5) on the left, and lungs of cortisone-treated rabbits of the same strains (IIIFIII 1-6 and III IIIC 1-4) on the right. These rabbits had inhaled aerosols of virulent human-type tubercle bacilli (H37Rv) 13 weeks previously. The cortisone treatment was started 9 days before infection and continued for 8 weeks during infection. Four and one-half weeks after the treatment was stopped, the rabbits were euthanized.

The cortisone-treated rabbit IIIFIII 1-6 (right) had two large thick-walled cavities in the right lung, one of which is shown in the photograph. The cortisone-treated rabbit III IIIC 1-4 (right) had numerous active tuberculous lesions in both lungs. The two control rabbits, however, had only a few minute regressing tubercles.

Although this experiment was similar to the one portrayed in Fig. 6, the inbred IIIFIII and III IIIC rabbits, which were genetically much more resistant than the inbred Ca rabbits in Fig. 6, developed fewer primary tubercles. These two factors, especially the native resistance of the host, evidently made the adverse effects of the glucocorticoids less severe.

Reproduced with permission from reference 2.

Citation: Dannenberg, Jr. A. 2006. Effects of Cortisone and Adrenocorticotropic Hormone on Tuberculosis, p 273-284. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555815684.ch16
1. Seyle, H. 1946. The general adaptation syndrome and the diseases of adaptation. J. Clin. Endocrinol. 6:117230.
2. Lurie, M. B.,, P. Zappasodi,, A. M. Dannenberg, Jr., and, E. Cardona-Lynch. 1953. Constitutional factors in resistance to infection: the effect of cortisone on the pathogenesis of tuberculosis, p. 8499. In G. Shwartzman (ed.), The Effect of ACTH and Cortisone upon Infection and Resistance. Columbia University Press, New York, N.Y.
3. Claman, H. N. 1983. Glucocorticosteroids I: anti-inflammatory mechanisms. Hosp. Pract. 18:123126, 131134.
4. Claman, H. N. 1983. Glucocorticosteroids II: the clinical responses. Hosp. Pract. 18:143146, 149151.
5. Dannenberg, A. M., Jr. 1979. The anti-inflammatory effects of glucocorticosteroids: a brief review of the literature. Inflammation 3:329343.
6. Lurie, M. B.,, P. Zappasodi,, A. M. Dannenberg, Jr., and, E. Cardone-Lynch. 1953. The effect of cortisone and ACTH on the pathogenesis of tuberculosis. Ann. N.Y. Acad. Sci. 56:779792.
7. Lurie, M. B.,, P. Zappasodi,, A. M. Dannenberg, Jr., and, I. B. Swartz. 1951. Constitutional factors in resistance to infection: the effect of cortisone on the pathogenesis of tuberculosis. Science 113:234237.
8. Lurie, M. B., and, P. Zappasodi. 1955. On the mode of action of cortisone on the pathogenesis of tuberculosis and its implications for the nature of genetic resistance to the disease, p. 246258. In Ciba Foundation Symposium on Experimental Tuberculosis. Churchill, London, United Kingdom.
9. Lurie, M. B. 1964. Resistance to Tuberculosis: Experimental Studies in Native and Acquired Defensive Mechanisms, p. 244264. Harvard University Press, Cambridge, Mass.
10. Kesavan, A. K.,, S. Mendez,, C. L. Hatem,, J. Lopez-Molina,, M. Brooks,, R. Fujiwara,, K. Aird,, M. L. M. Pitt,, A. M. Dannenberg, Jr., and, Y. C. Manabe. 2005. Effects of dexamethasone and transient malnutrition on rabbits infected with aerosolized Mycobacterium tuberculosis CDC1551. Infect. Immun. 73:70567060.
11. McCue, R. E.,, A. M. Dannenberg, Jr.,, S. Higuchi, and, M. Sugimoto. 1978. The effect of cortisone on the accumulation, activation, and necrosis of macrophages in tuberculous lesions. Inflammation 3:159176.
12. Yarborough, D. J.,, O. T. Meyer,, A. M. Dannenberg, Jr., and, B. Pearson. 1967. Histo-chemistry of macrophage hydrolases. III. Studies on β-galactosidase, β-glucuronidase and aminopeptidase with indolyl and naphthyl substrates. J. Reticuloendothel. Soc. 4:390408.
13. Dannenberg, A. M., Jr.,, O. T. Meyer,, J. R. Esterly, and, T. Kambara. 1968. The local nature of immunity in tuberculosis, illustrated histochemically in dermal BCG lesions. J. Immunol. 100:931941.
14. Dannenberg, A. M., Jr. 1968. Cellular hyper-sensitivity and cellular immunity in the pathogenesis of tuberculosis: specificity, systemic and local nature, and associated macrophage enzymes. Bacteriol. Rev. 32:85102.
15. Johnson, J. R., and, W. N. Davey. 1954. Cortisone, corticotropin, and antimicrobial therapy in tuberculosis in animals and man: a review. Am. Rev. Tuberc. 70:623636.
16. Spink, W. W. 1957. ACTH and adrenocorticosteroids as therapeutic adjuncts in infectious diseases. N. Engl. J. Med. 257:979983 (continued).
17. Spink, W. W. 1957. ACTH and adrenocorticosteroids as therapeutic adjuncts in infectious diseases. N. Engl. J. Med. 257:10311035 (concluded).
18. Silverstein, R., and, D.C. Johnson. 2003. Endogenous vs exogenous glucocorticoid responses to experimental bacterial sepsis. J. Leukoc. Biol. 73:417427.
19. Webster, J. I., and, E. M. Sternberg. 2004. Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in the toxic sequelae of exposure to bacterial and viral products. J. Endocrinol. 181:207221.
20. Webster, J. I.,, L. Tonelli, and, E. M. Sternberg. 2002. Neuroendocrine regulation of immunity. Annu. Rev. Immunol. 20:125163.
21. Nathan, C. 2002. Points of control in inflammation. Nature 420:846852.
22. Hernandez-Pando, R.,, M. de la Luz Streber,, H. Orozco,, K. Arriaga,, L. Pavon,, S. A. Al-Nakhli, and, G. A. W. Rook. 1998. The effects of androstenediol and dehydroepiandrosterone on the course and cytokine profile of tuberculosis in BALB/c mice. Immunology 95:234241.
23. Kass, E. H.,, O. Hechter,, T. W. Mou, and, M. B. Lurie. 1955. Effects of adrenal steroids on resistance to infection. Differences in the relative amounts of corticosterone and hydrocortisone secreted and their biologic effects. Arch. Intern. Med. 96:397402.

Tables

Generic image for table
TABLE 1

Effects of cortisone on tuberculosis produced by the inhalation of human-type tubercle bacilli (H37Rv) 5 weeks previously a

Citation: Dannenberg, Jr. A. 2006. Effects of Cortisone and Adrenocorticotropic Hormone on Tuberculosis, p 273-284. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch16
Generic image for table
TABLE 2

Effects of adrenocorticotropic hormone (ACTH) on tuberculosis produced by the inhalation of human-type tubercle bacilli (H37Rv) a

Citation: Dannenberg, Jr. A. 2006. Effects of Cortisone and Adrenocorticotropic Hormone on Tuberculosis, p 273-284. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch16

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error