Warning: mkdir(): Permission denied in /home/virtual/lib/view_data.php on line 81

Warning: fopen(upload/ip_log/ip_log_2024-12.txt): failed to open stream: No such file or directory in /home/virtual/lib/view_data.php on line 83

Warning: fwrite() expects parameter 1 to be resource, boolean given in /home/virtual/lib/view_data.php on line 84
Study on the therapeutic effects of interferon and gamma-globulin in experimental Pneumocystis carinii pneumonia
| Home | E-Submission | Sitemap | Contact us |  
top_img
Korean J Parasito Search

CLOSE

Korean J Parasito > Volume 30(3):1992 > Article

Original Article
Korean J Parasitol. 1992 Sep;30(3):219-226. Korean.
Published online Mar 20, 1994.  http://dx.doi.org/10.3347/kjp.1992.30.3.219
Copyright © 1992 by The Korean Society for Parasitology
Study on the therapeutic effects of interferon and gamma-globulin in experimental Pneumocystis carinii pneumonia
Dae-Whan Shin,Dae-Young Kang,*Young-Ha Lee,Young-Eun Na and Keon-Jung Yun
Department of Parasitology, College of Medicine, Chungnam National University, Taejon 301-131, Korea.
*Department of Pathology, College of Medicine, Chungnam National University, Taejon 301-131, Korea.
Abstract

This study was performed to observe the therapeutic effects of interferon-gamma(IFN-γ) and gamma-globulin(γ-globulin) in experimental Pneumocystis carinii pneumonia of immune suppressed mice. After 9 weeks, trimethoprim-sulfamethoxazole(TMP-SMZ; 10-50 mg/mouse/day), mouse IFN-γ(5 × 104 units/mouse/day) and mouse γ-globulin(20 mg/mouse/day) were administered to the mice for 3 weeks by the experimental group. The therapeutic efficacy was evaluated by body weights, histopathologic and electron microscopic findings of the lungs, and number of P. carinii cysts by Gomori's methenamine silver stain. Body weights of the mice were significantly increased in the group of combination therapy of TMP-SMZ with IFN-γ or γ-globulin, and in the group of TMP-SMZ treatment (p < 0.05), however, little effect was found in the group of γ-globulin alone. Histopathologic findings of P. carinii pneumonia were much improved in the group of combination therapy of TMP-SMZ with IFN-γ. Treatment with either TMP-SMZ or IFN-γ significantly reduced the number of cysts in the P. carinii pneumonia, but γ-globulin alone was ineffective. In electron microscopic findings of P. carinii pneumonia, the number of trophozoites and cysts were reduced by treatment with either TMP-SMZ or IFN-γ, and most of the cysts were empty or containing one or two intracystic bodies. The present results suggested, that combination therapy of TMP-SMZ with IFN-γ had synergistic effects in treatment of P. carinii pneumonia in experimental mice.

Figures


Fig. 1
Changes of body weights of mice after anti-P. carinii therapy; each point represents the mean of 5 mice.

NOTE: I. C., infected control; Group 1, administered with trimethoprim-sulfameth-oxazole (TMP-SMZ); Group 2, administered with TMP-SMZ and mouse interferon-gamma (IFN-γ); Group 3, administered with IFN-γ; Group 4, administered with TMP-SMZ and mouse gamma-globulin (γ-globulin); Group 5, administered with γ-globulin.



Fig. 2
Changes of infectivity score of P. carinii in mice after anti-P. carinii therapy; Each bar repersents the mean±S.E. of 5 mice.

*Infectivity score: refer to Table 1

NOTE: refer to Fig. 1.


Tables


Table 1
Changes of body weight and infectivity score of P. carinii in mice injected with cortisone acetate (2.5mg twice a week)


Table 2
Changes of body weights after administration of different treatment regimens for 3 weeks on P. carinii pneumonia in mice


Table 3
Histopathologic findings of the lungs with P. carinii pneumonia in mice after anti-P. carinii therapy

References
1. Shin DW, Lee YH, Na YE. [An experimental study on prednisolone-induced interstitial pneumonia caused by Pneumocystis carinii]. Korean J Parasitol 1989;27(2):101–108.
 
2. Allegra CJ, Kovacs JA, Drake JC, Swan JC, Chabner BA, Masur H. Activity of antifolates against Pneumocystis carinii dihydrofolate reductase and identification of a potent new agent. J Exp Med 1987;165(3):926–931.
  
3. Bartlett MS, Fishman JA, Queener SF, Durkin MM, Jay MA, Smith JW. New rat model of Pneumocystis carinii infection. J Clin Microbiol 1988;26(6):1100–1102.
 
4. Bonagura VR, Cunningham-Rundles S, Edwards BL, Ilowite NT, Wedgwood JF, Valacer DJ. Common variable hypogammaglobulinemia, recurrent Pneumocystis carinii pneumonia on intravenous gamma-globulin therapy, and natural killer deficiency. Clin Immunol Immunopathol 1989;51(2):216–231.
  
5. Burke BA. Pneumocystis carinii infection: diagnosis and pathogenesis. Natl Cancer Inst Monogr 1976;43:151–156.
 
6. Campbell WG Jr. Ultrastructure of Pneumocystis in human lung. Life cycle in human pneumocystosis. Arch Pathol 1972;93(4):312–324.
 
7. Cushion MT, Stanforth D, Linke MJ, Walzer PD. Method of testing the susceptibility of Pneumocystis carinii to antimicrobial agents in vitro. Antimicrob Agents Chemother 1985;28(6):796–801.
 
8. Dauzier G, Willis T, Barnett RN. Pneumocystis carinii pneumonia in an infant. Am J Clin Pathol 1956;26(7):787–793.
 
9. DeVita VT Jr, Broder S, Fauci AS, Kovacs JA, Chabner BA. Developmental therapeutics and the acquired immunodeficiency syndrome. Ann Intern Med 1987;106(4):568–581.
 
10. Fauci AS, Dale DC, Balow JE. Glucocorticosteroid therapy: mechanisms of action and clinical considerations. Ann Intern Med 1976;84(3):304–315.
 
11. Fauci AS, Macher AM, Longo DL, Lane HC, Rook AH, Masur H, Gelmann EP. NIH conference. Acquired immunodeficiency syndrome: epidemiologic, clinical, immunologic, and therapeutic considerations. Ann Intern Med 1984;100(1):92–106.
 
12. Frenkel JK, Good JT, Shultz JA. Latent Pneumocystis infection of rats, relapse, and chemotherapy. Lab Invest 1966;15(10):1559–1577.
 
13. Furuta T, Ueda K, Fujiwara K, Yamanouchi K. Cellular and humoral immune responses of mice subclinically infected with Pneumocystis carinii. Infect Immun 1985;47(2):544–548.
 
14. Garner RE, Kuruganti U, Czarniecki CW, Chiu HH, Domer JE. In vivo immune responses to Candida albicans modified by treatment with recombinant murine gamma interferon. Infect Immun 1989;57(6):1800–1808.
 
15. Hasleton PS, Curry A, Rankin EM. Pneumocystis carinii pneumonia: a light microscopical and ultrastructural study. J Clin Pathol 1981;34(10):1138–1146.
  
16. Herberman RB. Design of clinical trials with biological response modifiers. Cancer Treat Rep 1985;69(10):1161–1164.
 
17. Hershman MJ, Polk HC Jr, Pietsch JD, Kuftinec D, Sonnenfeld G. Modulation of Klebsiella pneumoniae infection of mice by interferon-gamma. Clin Exp Immunol 1988;72(3):406–409.
 
18. Hughes WT, Kim HK, Price RA, Miller C. Attempts at prophylaxis for murine Pneumocystis carinii pneumonitis. Curr Ther Res Clin Exp 1973;15(8):581–587.
 
19. Hughes WT, McNabb PC, Makres TD, Feldman S. Efficacy of trimethoprim and sulfamethoxazole in the prevention and treatment of Pneumocystis carinii pneumonitis. Antimicrob Agents Chemother 1974;5(3):289–293.
 
20. Hughes WT. Current status of laboratory diagnosis of Pneumocystis carinii pneumonitis. CRC Crit Rev Clin Lab Sci 1975;6(2):145–170.
  
21. Hughes WT, Feldman S, Chaudhary SC, Ossi MJ, Cox F, Sanyal SK. Comparison of pentamidine isethionate and trimethoprim-sulfamethoxazole in the treatment of Pneumocystis carinii pneumonia. J Pediatr 1978;92(2):285–291.
  
22. Ivady G, et al. Lancet 1967;1:616–617.
  
23. Jahiel RI, Vilcek J, Nussenzweig RS. Exogenous interferon protects mice against Plasmodium berghei malaria. Nature 1970;227(5265):1350–1351.
  
24. Krugman S. The clinical use of gamma globulin. N Engl J Med 1963;269:195–201.
  
25. Kurimoto T, Yoneyama H, Sato K, Okachi R. [Combined effects of astromicin and human gamma-globulin prepared for intravenous use]. Jpn J Antibiot 1987;40(2):303–310.
 
26. Matthes J, Walker LA, Watson JG, Bird AG. AIDS encephalopathy with response to treatment. Arch Dis Child 1988;63(5):545–547.
  
27. Pesanti EL. Interaction of cytokines and alveolar cells with Pneumocystis carinii in vitro. J Infect Dis 1991;163(3):611–616.
  
28. Schellekens H. Animal models in interferon research: some current trends. Experientia 1989;45(6):558–562.
  
29. Schijns VE, Borman TH, Schellekens H, Horzinek MC. Antiviral activity of recombinant rat interferon gamma in immunologically impaired and immunosuppressed rats. J Gen Virol 1988;69(Pt 8):1979–1985.
  
30. Shear HL, Valladares G, Narachi MA. Enhanced treatment of Pneumocystis carinii pneumonia in rats with interferon-gamma and reduced doses of trimethoprim/sulfamethoxazole. J Acquir Immune Defic Syndr 1990;3(10):943–948.
 
31. Sheldon WH. Experimental pulmonary Pneumocystis carinii infection in rabbits. J Exp Med 1959;110(1):147–160.
  
32. Sheldon WH. Pulmonary Pneumocystis carinii infection. J Pediatr 1962;61:780–791.
  
33. Suzuki Y, Conley FK, Remington JS. Treatment of toxoplasmic encephalitis in mice with recombinant gamma interferon. Infect Immun 1990;58(9):3050–3055.
 
34. Walzer PD, Powell RD Jr, Yoneda K. Experimental Pneumocystis carinii pneumonia in different strains of cortisonized mice. Infect Immun 1979;24(3):939–947.
 
35. Walzer PD, LaBine M, Redington TJ, Cushion MT. Lymphocyte changes during chronic administration of and withdrawal from corticosteroids: relation to Pneumocystis carinii pneumonia. J Immunol 1984;133(5):2502–2508.
 
36. Weller R. [Production of pneumocystoses in experiments with animals]. Z Kinderheilkd 1955;76(4):366–378.
  
37. Wharton JM, Coleman DL, Wofsy CB, Luce JM, Blumenfeld W, Hadley WK, Ingram-Drake L, Volberding PA, Hopewell PC. Trimethoprim-sulfamethoxazole or pentamidine for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A prospective randomized trial. Ann Intern Med 1986;105(1):37–44.
 
38. Yoneda K, Walzer PD. Mechanism of pulmonary alveolar injury in experimental Pneumocystis carinii pneumonia in the rat. Br J Exp Pathol 1981;62(4):339–346.
 
Editorial Office
Department of Molecular Parasitology, Samsung Medical Center, School of Medicine, Sungkyunkwan University,
2066 Seobu-ro, Jangan-gu, Suwon 16419, Gyeonggi-do, Korea.
Tel: +82-31-299-6251   FAX: +82-1-299-6269   E-mail: kjp.editor@gmail.com
About |  Browse Articles |  Current Issue |  For Authors and Reviewers
Copyright © 2024 by The Korean Society for Parasitology and Tropical Medicine.     Developed in M2PI