Details

Autor(en) / Beteiligte

• Grau, Georges E.
• Heremans, Hubertine
• Piguet, Pierre-François
• Pointaire, Pascal
• Lambert, Paul-Henri
• Billiau, Alfons
• Vassalli, Pierre

Titel

Monoclonal Antibody against Interferon γ Can Prevent Experimental Cerebral Malaria and its Associated Overproduction of Tumor Necrosis Factor

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1989-07, Vol.86 (14), p.5572-5574

Ort / Verlag

Washington, DC: National Academy of Sciences of the United States of America

Erscheinungsjahr

1989

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 γ , 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 γ constitutes an important link in the cytokine network that leads to brain vessel inflammation in experimental malaria. It is proposed that interferon γ released by activated CD4+ T cells acts by augmenting both production and action of tumor necrosis factor.