Treatment of toxoplasmic encephalitis in mice with recombinant gamma interferon

The effect of exogenous gamma interferon (IFN-gamma) on toxoplasmic encephalitis in a murine model was evaluated. The brains of CBA/Ca mice chronically infected with the ME49 strain of Toxoplasma gondii have a remarkable inflammatory cell infiltrate. Intravenous administration of six doses (5 x 10(5) U each) of recombinant IFN-gamma (rIFN-gamma) resulted in a remarkable decrease in numbers and foci of inflammatory cells in murine brain parenchyma and perivascular areas 1 day after the last injection of IFN-gamma. Immunoperoxidase staining revealed the presence of tachyzoites only on areas of acute focal inflammation, suggesting that the focal inflammation was caused by the proliferation of tachyzoites. The remarkable reduction in number of foci of acute focal inflammation in the brains of the IFN-gamma-treated mice indicates that the treatment resulted in diminished numbers of tachyzoites in the brains of the infected mice. The effect of rIFN-gamma was dose dependent; injection of 5 x 10(5) U every other day for a total of six doses was effective; injection of either 5 x 10(4), 5 x 10(3), or 5 x 10(2) U was not. This therapeutic effect of rIFN-gamma on encephalitis was not present 2 weeks after the last injection of rIFN-gamma. At that time, mice again had severe inflammation in their brains. Toxoplasma antibody production was not affected by treatment with rIFN-gamma. These results offer support for the value of injection of IFN-gamma in the treatment of toxoplasmic encephalitis in immunosuppressed patients, although its effect appears to be transient.

[1]  J. Schwartzman,et al.  Murine gamma interferon fails to inhibit Toxoplasma gondii growth in murine fibroblasts , 1990, Infection and immunity.

[2]  Y. Suzuki,et al.  Importance of endogenous IFN-gamma for prevention of toxoplasmic encephalitis in mice. , 1989, Journal of immunology.

[3]  Y. Suzuki,et al.  Differences in virulence and development of encephalitis during chronic infection vary with the strain of Toxoplasma gondii. , 1989, The Journal of infectious diseases.

[4]  H. Murray,et al.  Role of tryptophan degradation in respiratory burst-independent antimicrobial activity of gamma interferon-stimulated human macrophages , 1989, Infection and immunity.

[5]  Y. Suzuki,et al.  Dual regulation of resistance against Toxoplasma gondii infection by Lyt-2+ and Lyt-1+, L3T4+ T cells in mice. , 1988, Journal of immunology.

[6]  R. Schreiber,et al.  Interferon-gamma: the major mediator of resistance against Toxoplasma gondii. , 1988, Science.

[7]  E. Borden,et al.  Biologic-response-modifier-induced indoleamine 2,3-dioxygenase activity in human peripheral blood mononuclear cell cultures. , 1987, Journal of immunology.

[8]  M. Edelstein,et al.  The actions of interferon and antiinflammatory agents of induction of indoleamine 2,3-dioxygenase in human peripheral blood monocytes. , 1987, Biochemical and biophysical research communications.

[9]  Meredith Jt,et al.  Toxoplasmosis of the central nervous system. , 1987, American family physician.

[10]  M. Kaplan,et al.  In vitro and in vivo activation of human mononuclear phagocytes by interferon-gamma. Studies with normal and AIDS monocytes. , 1987, Journal of immunology.

[11]  V. Brinkmann,et al.  Different regulation of the L3T4-T cell subset by B cells in different mouse strains bearing the H-2k haplotype. , 1986, Journal of immunology.

[12]  G. Byrne,et al.  Induction of tryptophan catabolism is the mechanism for gamma-interferon-mediated inhibition of intracellular Chlamydia psittaci replication in T24 cells , 1986, Infection and immunity.

[13]  H. Winkler,et al.  Gamma-interferon-induced inhibition of the growth of Rickettsia prowazekii in fibroblasts cannot be explained by the degradation of tryptophan or other amino acids , 1986, Infection and immunity.

[14]  P. Erb,et al.  In vitro cultivation of Toxoplasma gondii cysts in astrocytes in the presence of gamma interferon , 1986, Infection and immunity.

[15]  H. Murray,et al.  Activation of tissue macrophages from AIDS patients: in vitro response of AIDS alveolar macrophages to lymphokines and interferon-gamma. , 1985, Journal of immunology.

[16]  D. Bredesen,et al.  Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): experience at UCSF and review of the literature. , 1985, Journal of neurosurgery.

[17]  J. Remington,et al.  Toxoplasma antigen isolated by affinity chromatography with monoclonal antibody protects mice against lethal infection with Toxoplasma gondii. , 1984, Journal of immunology.

[18]  B. Luft,et al.  Effect of murine interferon gamma on murine toxoplasmosis. , 1984, The Journal of infectious diseases.

[19]  H. Masur,et al.  Impaired production of lymphokines and immune (gamma) interferon in the acquired immunodeficiency syndrome. , 1984, The New England journal of medicine.

[20]  E. Pfefferkorn.  Interferon gamma blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[21]  J. Remington,et al.  Toxoplasma gondii infection of the central nervous system. Use of the peroxidase-antiperoxidase method to demonstrate toxoplasma in formalin fixed, paraffin embedded tissue sections. , 1981, Human pathology.

[22]  J. Remington,et al.  Direct agglutination test for diagnosis of Toxoplasma infection: method for increasing sensitivity and specificity , 1980, Journal of clinical microbiology.

[23]  J. Remington,et al.  The use of killed vaccines in immunization against an intracellular parasite: Toxoplasma gondii. , 1972, Journal of immunology.

[24]  B. Luft,et al.  Toxoplasmosis of the central nervous system. , 1991 .

[25]  B. Luft,et al.  AIDS commentary. Toxoplasmic encephalitis. , 1988, The Journal of infectious diseases.

[26]  D. Armstrong,et al.  Central-Nervous-System Toxoplasmosis in Homosexual Men and Parenteral Drug Abusers , 1984 .