Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1994 Jul;62(7):2773–2778. doi: 10.1128/iai.62.7.2773-2778.1994

Antibody against interleukin-6 reduces inflammation and numbers of cysts in brains of mice with toxoplasmic encephalitis.

Y Suzuki 1, Q Yang 1, F K Conley 1, J S Abrams 1, J S Remington 1
PMCID: PMC302880  PMID: 8005667

Abstract

Treatment of toxoplasmic encephalitis in C57BL/6 mice with monoclonal antibody (MAb) against interleukin-6 (IL-6) resulted in a remarkable decrease in the number of foci of acute inflammation in their brains caused by proliferation of tachyzoites. In brains of mice treated with isotype control MAb and those treated with anti-IL-6 MAb, tachyzoites were observed only in foci of acute inflammation. Immunoperoxidase staining revealed a greatly diminished frequency of tachyzoites in brains of mice treated with anti-IL-6 MAb. Of interest, treatment with MAb against IL-6 was also associated with reduced numbers of Toxoplasma gondii cysts in the brains and with higher serum levels of gamma interferon than in control mice. Paradoxically, the mice treated with anti-IL-6 MAb had higher serum levels of IL-6 as measured by an enzyme-linked immunosorbent assay than controls. These results revealed the importance of IL-6 in the immunopathogenesis of murine toxoplasmic encephalitis.

Full text

PDF
2777

Images in this article

2775Image
on p.2775
2776Image
on p.2776

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cherwinski H. M., Schumacher J. H., Brown K. D., Mosmann T. R. Two types of mouse helper T cell clone. III. Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally monospecific bioassays, and monoclonal antibodies. J Exp Med. 1987 Nov 1;166(5):1229–1244. doi: 10.1084/jem.166.5.1229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Conley F. K., Jenkins K. A., Remington J. S. Toxoplasma gondii infection of the central nervous system. Use of the peroxidase-antiperoxidase method to demonstrate toxoplasma in formalin fixed, paraffin embedded tissue sections. Hum Pathol. 1981 Aug;12(8):690–698. doi: 10.1016/s0046-8177(81)80170-0. [DOI] [PubMed] [Google Scholar]
  3. Gazzinelli R. T., Eltoum I., Wynn T. A., Sher A. Acute cerebral toxoplasmosis is induced by in vivo neutralization of TNF-alpha and correlates with the down-regulated expression of inducible nitric oxide synthase and other markers of macrophage activation. J Immunol. 1993 Oct 1;151(7):3672–3681. [PubMed] [Google Scholar]
  4. Gazzinelli R., Xu Y., Hieny S., Cheever A., Sher A. Simultaneous depletion of CD4+ and CD8+ T lymphocytes is required to reactivate chronic infection with Toxoplasma gondii. J Immunol. 1992 Jul 1;149(1):175–180. [PubMed] [Google Scholar]
  5. Heremans H., Dillen C., Put W., Van Damme J., Billiau A. Protective effect of anti-interleukin (IL)-6 antibody against endotoxin, associated with paradoxically increased IL-6 levels. Eur J Immunol. 1992 Sep;22(9):2395–2401. doi: 10.1002/eji.1830220932. [DOI] [PubMed] [Google Scholar]
  6. Levy R. M., Bredesen D. E., Rosenblum M. L. Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): experience at UCSF and review of the literature. J Neurosurg. 1985 Apr;62(4):475–495. doi: 10.3171/jns.1985.62.4.0475. [DOI] [PubMed] [Google Scholar]
  7. Lu Z. Y., Brochier J., Wijdenes J., Brailly H., Bataille R., Klein B. High amounts of circulating interleukin (IL)-6 in the form of monomeric immune complexes during anti-IL-6 therapy. Towards a new methodology for measuring overall cytokine production in human in vivo. Eur J Immunol. 1992 Nov;22(11):2819–2824. doi: 10.1002/eji.1830221110. [DOI] [PubMed] [Google Scholar]
  8. Luft B. J., Remington J. S. Toxoplasmic encephalitis in AIDS. Clin Infect Dis. 1992 Aug;15(2):211–222. doi: 10.1093/clinids/15.2.211. [DOI] [PubMed] [Google Scholar]
  9. May L. T., Neta R., Moldawer L. L., Kenney J. S., Patel K., Sehgal P. B. Antibodies chaperone circulating IL-6. Paradoxical effects of anti-IL-6 "neutralizing" antibodies in vivo. J Immunol. 1993 Sep 15;151(6):3225–3236. [PubMed] [Google Scholar]
  10. Starnes H. F., Jr, Pearce M. K., Tewari A., Yim J. H., Zou J. C., Abrams J. S. Anti-IL-6 monoclonal antibodies protect against lethal Escherichia coli infection and lethal tumor necrosis factor-alpha challenge in mice. J Immunol. 1990 Dec 15;145(12):4185–4191. [PubMed] [Google Scholar]
  11. Suzuki Y., Conley F. K., Remington J. S. Importance of endogenous IFN-gamma for prevention of toxoplasmic encephalitis in mice. J Immunol. 1989 Sep 15;143(6):2045–2050. [PubMed] [Google Scholar]
  12. Suzuki Y., Conley F. K., Remington J. S. Treatment of toxoplasmic encephalitis in mice with recombinant gamma interferon. Infect Immun. 1990 Sep;58(9):3050–3055. doi: 10.1128/iai.58.9.3050-3055.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Suzuki Y., Orellana M. A., Schreiber R. D., Remington J. S. Interferon-gamma: the major mediator of resistance against Toxoplasma gondii. Science. 1988 Apr 22;240(4851):516–518. doi: 10.1126/science.3128869. [DOI] [PubMed] [Google Scholar]
  14. Suzuki Y., Orellana M. A., Wong S. Y., Conley F. K., Remington J. S. Susceptibility to chronic infection with Toxoplasma gondii does not correlate with susceptibility to acute infection in mice. Infect Immun. 1993 Jun;61(6):2284–2288. doi: 10.1128/iai.61.6.2284-2288.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Wong B., Gold J. W., Brown A. E., Lange M., Fried R., Grieco M., Mildvan D., Giron J., Tapper M. L., Lerner C. W. Central-nervous-system toxoplasmosis in homosexual men and parenteral drug abusers. Ann Intern Med. 1984 Jan;100(1):36–42. doi: 10.7326/0003-4819-100-1-36. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES