Polyclonal anti-tumor necrosis factor-alpha Fab used as an ancillary treatment for severe malaria
| Autor: | Sornchai Looareesuwan, Frank Hills, David A. Warrell, L Sjöström, Polrat Wilairatana, R S Porter, Srivicha Krudsood |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Artesunate Pilot Projects Parasitemia Pharmacology chemistry.chemical_compound Malaria Falciparum Immunoassay biology Mefloquine Immunoglobulin Fab Fragments Middle Aged Intercellular Adhesion Molecule-1 Artemisinins Infectious Diseases Area Under Curve Female Antibody Sesquiterpenes medicine.drug Adult Adolescent Plasmodium falciparum Antimalarials Interferon-gamma Virology medicine Animals Humans Adverse effect Aged business.industry Interleukin-6 Tumor Necrosis Factor-alpha Interleukin-8 medicine.disease biology.organism_classification Kinetics chemistry Immunology Serum sickness biology.protein Interleukin-2 Parasitology business Interleukin-1 |
| Zdroj: | The American journal of tropical medicine and hygiene. 61(1) |
| ISSN: | 0002-9637 |
| Popis: | Single doses (250, 500, 1,000, or 2,000 units/kg) of an ovine polyclonal-specific Fab fragment directed against tumor necrosis factor-alpha (TNF-alpha) were given to 17 adult patients with severe falciparum malaria immediately before treatment with artesunate in a pilot study to assess safety and optimal dosage with a view to future studies. Clinical and laboratory variables were compared with 11 controls. In the groups given Fab, there was a tendency for a faster resolution of clinical manifestations and reduction of fever but also a tendency towards longer parasite clearance times. Adverse events were more common in the control group and no early anaphylactic or late serum sickness reactions occurred in the Fab treated patients. On admission all patients had markedly elevated levels of TNF-alpha (85-1,532 ng/L) and interleukin-6 (IL-6) (30-27,500 ng/L). Also, 86% had elevated interferon-gamma (IFN-gamma) levels, 75% had increased IL-2 levels, 36% had increased IL-8 levels, and 21% had increased IL-1beta levels. Antibody treatment reduced IFN-gamma concentrations in a dose-related manner, but had no obvious effects on levels of other cytokines in this small study, although unbound TNF-alpha was undetectable after Fab treatment. Circulating concentrations of soluble E-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were not affected by Fab treatment. The Fab exhibited a two-compartment, dose-proportional kinetics with an average elimination half-life of 12.0 hr, with about 20% being excreted renally. These results encourage a randomized, placebo-controlled trial in patients with cerebral malaria and provide some guidance about dosage. |
| Databáze: | OpenAIRE |
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