Interleukin 6 production in experimental cerebral malaria: modulation by anticytokine antibodies and possible role in hypergammaglobulinemia.
The production of Interleukin 6 (IL-6) was studied during experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA (PbA) infection. IL-6 is present in the serum of mice with ECM, the highest concentrations being observed in mice with full-blown neurological syndrome. High IL-6 levels were also observed, however, in the absence of pathology in nonlethal malaria infection. These data suggest that IL-6 is produced in large amounts during malaria infection, but does not play a major role in the pathogenesis of ECM. A modulation of IL-6 production in ECM was achieved by in vivo treatment with other anticytokine antibodies: antibodies to interferon (IFN-gamma) or to tumor necrosis factor (TNF) abolished the rise of IL-6, while anti-IL-3 and anti-granulocyte/macrophage colony-stimulating factor antibodies only partially prevented this rise, suggesting that the two cytokines IFN-gamma and TNF are important intermediates in IL-6 production. Passive immunization against IL-6 did not prevent ECM, but significantly reduced serum IgG levels in malaria-infected mice. Thus, by its effects on B cells, IL-6 may be involved in hypergammaglobulinemia and immune-complex diseases, e.g., glomerulonephritis observed during malaria infection.
Grau
G E
GE
Department of Pathology, University of Geneva, Switzerland.
Frei
K
K
Piguet
P F
PF
Fontana
A
A
Heremans
H
H
Billiau
A
A
Vassalli
P
P
Lambert
P H
PH
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000502:physiology; D001927:Brain Diseases / Q000097:blood / Q000469:parasitology*; D016207:Cytokines / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006942:Hypergammaglobulinemia / Q000209:etiology / Q000503:physiopathology; D007074:Immunoglobulin G / Q000032:analysis; D007371:Interferon-gamma / Q000276:immunology; D007377:Interleukin-3 / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood* / Q000276:immunology; D008288:Malaria / Q000097:blood* / Q000209:etiology / Q000469:parasitology; D051379:Mice; D010962:Plasmodium berghei / Q000302:isolation & purification; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000906:Antibodies; D016207:Cytokines; D007074:Immunoglobulin G; D007377:Interleukin-3; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor