Monoclonal antibody against interferon gamma can prevent experimental cerebral malaria and its associated overproduction of tumor necrosis factor.
Experimental cerebral malaria (ECM), a lethal hyperacute neurological syndrome associated with high blood levels of tumor necrosis factor, develops in genetically susceptible (CBA/Ca) mice 7 days after infection with Plasmodium berghei ANKA strain. Injections of neutralizing monoclonal antibody against recombinant murine interferon gamma, not later than 4 days after infection, markedly reduced the incidence of ECM and the elevation in serum levels of tumor necrosis factor. This treatment prevented the cerebral lesions (plugging of brain vessels by monocytes, lymphocytes, and parasitized erythrocytes). In contrast, the extent of macrophage infiltration in lymphoid organs (which is a characteristic feature of mice developing ECM), as well as the course of infection, remained unaffected by the antibody treatment. Protected mice died at a later time of severe anemia and overwhelming parasitemia, the usual outcome of P. berghei infection in mice that are not susceptible to ECM. The present data indicate that interferon gamma constitutes an important link in the cytokine network that leads to brain vessel inflammation in experimental malaria. It is proposed that interferon gamma released by activated CD4+ T cells acts by augmenting both production and action of tumor necrosis factor.
Grau
G E
GE
Department of Pathology, University of Geneva, Switzerland.
Heremans
H
H
Piguet
P F
PF
Pointaire
P
P
Lambert
P H
PH
Billiau
A
A
Vassalli
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001927:Brain Diseases / Q000517:prevention & control*; D004198:Disease Susceptibility; D005260:Female; D007371:Interferon-gamma / Q000276:immunology*; D008264:Macrophages / Q000502:physiology; D008288:Malaria / Q000517:prevention & control*; D051379:Mice; D008808:Mice, Inbred CBA; D010962:Plasmodium berghei; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma