Protection of mice from malaria after co-administration of recombinant mouse granulocyte-macrophage colony- stimulating factor and methionine-enkephalin.
The protective effect of co-administration of recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and synthetic peptide met-enkephalin (M-ENK) against blood-induced Plasmodium berghei infection in Swiss mice was investigated. Mice co-administered with rmGM-CSF (10.0 mug/kg) and M-ENK (2.0 mg/kg) x 3/day, i.p., beginning on day -1 and continuing through day +4 after the initiation of infection, showed significant suppression (p < 0.05) (sometimes even complete elimination) of parasitaemia compared to vehicle-treated controls. However, when administered separately, neither of these agents induced any detectable protective effect. Surprisingly, mice similarly co-administered with rmGM-CSF (10.0 mug/kg) and higher doses of M-ENK (10.0 mg/kg), showed no protection. Polyclonal neutralizing (100%) antibody to rmGM-CSF abrogated the combined protective effect of these agents. Additionally, naloxone (10.0 mg/kg/day x 6, i.p.), a non-selective, opioid receptor antagonist, also blocked the combined protection. Mice that survived the challenge showed a significant increase (p < 0.05) in total circulating leukocytes counts, and the pool-size and the phagocytic activity of both the peritoneal and splenic macrophages, ex vivo. Silica (3.0 mg/mouse, i.v.) abrogated the combined protective effect of rmGM-CSF and M-ENK. These results indicate that co-administration of rmGM-CSF and dose dependent quantities of M-ENK in P. berghei-infected mice can protect against malaria, apparently through macrophage-mediated mechanisms.
Singh
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PP
Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector-67, Phase-X, SAS Nagar-160 062, India. ppsingh@mailmetoday.com
Singh
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D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D004338:Drug Combinations; D004744:Enkephalin, Methionine / Q000008:administration & dosage*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000276:immunology; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D010962:Plasmodium berghei; D011994:Recombinant Proteins; D012822:Silicon Dioxide / Q000494:pharmacology
D000906:Antibodies; D004338:Drug Combinations; D011994:Recombinant Proteins; D009270:Naloxone; D004744:Enkephalin, Methionine; D012822:Silicon Dioxide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor