A synthetic tumor necrosis factor-alpha agonist peptide enhances human polymorphonuclear leukocyte-mediated killing of Plasmodium falciparum in vitro and suppresses Plasmodium chabaudi infection in mice.

Kumaratilake, L.M.; Rathjen, Deborah A.; Mack, P; Widmer, Fred; Prasertsiriroj, Varee; Fèrrante, Antonio

doi:10.1172/jci117923

Cited by 23 publications

(36 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They concluded that host-protective effects of TNF can be retained, while the toxic effects are eliminated using a selected characterized subunit of the cytokine. 24 In conclusion, our findings established that TNFα levels are elevated in patients with Falciparum malaria. Our data provide further confirmation of the clinical association between elevated TNFα levels and several different manifestations of severe P. falciparum infection, particularly anemia, hepatic and kidney dysfunction.…”

Section: Discussionsupporting

confidence: 63%

Tumor Necrosis Factor in Falciparum Malaria

Gandapur

Malik

1996

Ann Saudi Med

View full text Add to dashboard Cite

To investigate the relationship of TNFα levels to Plasmodium falciparum (PF) infection, plasma TNFα concentrations were measured in Pakistani adults and children with mild, severe, cerebral and chronic falciparum malaria and healthy (control) subjects. The initial geometric mean plasma concentrations of TNFα in adult patients with severe malaria (187.6 pg/mL) were significantly higher than mild malaria patients (87.1 pg/mL, P < 0.001). TNFα levels were not correlated to parasite density, cerebral malaria, young age, hypoglycemia or fatal outcome; however, they were associated with severe anemia, and hepatic and kidney dysfunction. TNFα levels were not significantly increased in 16 patients with hyperparasitemia and were significantly elevated (P < 0.02) in chronic malaria patients as compared to control subjects. TNFα levels were elevated independently in patients with anemia, hypoglycemia (P < 0.001, P < 0.05), and hepatic and kidney (P < 0.001 each) dysfunction. In this study, high TNFα levels were associated with several manifestations of severe malaria and were not specific to cerebral malaria and hyperparasitemia.

show abstract

Section: Discussionsupporting

confidence: 63%

Tumor Necrosis Factor in Falciparum Malaria

Gandapur

Malik

1996

Ann Saudi Med

View full text Add to dashboard Cite

show abstract

“…TNFα suppresses P. chabaudi chabaudi in mice (24), and TNF-R1 knockout mice are more susceptible to this infection (25). TNFα also increases clearance of plasmodium infection by macrophages (26) and enhances killing of P. falciparum and P. vivax through the actions of intermediates such as nitric oxide (27)-nitric oxide, in turn, correlates with resistance in children infected with P. falciparum (28).…”

Section: Discussionmentioning

confidence: 99%

A defunctioning polymorphism in FCGR2B is associated with protection against malaria but susceptibility to systemic lupus erythematosus

Willcocks

Carr

Niederer

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

183

141

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease more prevalent in people of African and Asian origin than Caucasian origin. FcγRIIb is an inhibitory Fc receptor with a critical role in immune regulation. Mouse data suggest that FcγRIIb deficiency increases susceptibility to autoimmune disease but protects against infection. We show that a SNP in human FCGR2B that abrogates receptor function is strongly associated with susceptibility to SLE in both Caucasians and Southeast Asians. The minor allele of this SNP is more common in Southeast Asians and Africans, populations from areas where malaria is endemic, than in Caucasians. We show that homozygosity for the minor allele is associated with substantial protection against severe malaria in an East African population (odds ratio = 0.56; P = 7

show abstract

“…The mechanisms of the synergistic priming effects of GM-CSF and TNF were not studied here. These cytokines while stimulating neutrophils via different receptors and different signal transduction mechanisms (Arnaout et al 1986, Lopez et al 1992, Ferrante, Hii & Rathjen 1995, Waterman & Sha'afi 1995 both give rise to increased expression of CR3 and Fc RIII on neutrophils (Buckle & Hogg 1989, Leino et al 1993, Kumaratilake et al 1995.…”

Section: Discussionmentioning

confidence: 99%

“…Cytokine therapy is in consideration for treatment of malignant and infectious diseases and it is evident from our results that the possible use of GM-CSF in subgroups of malaria patients could be of benefit. Although the use of cytokine therapy at present has been limited by the cost and by some of the toxic effects, muteins or synthetic subunit cytokines with reduced toxicity may pave the way for future cytokine therapy (Kumaratilake et al 1995).…”

Section: Discussionmentioning

confidence: 99%

GM‐CSF‐induced priming of human neutrophils for enhanced phagocytosis and killing of asexual blood stages of Plasmodium falciparum: synergistic effects of GM‐CSF and TNF

Kumaratilake

Fèrrante

Jaeger

et al. 1996

Parasite Immunology

View full text Add to dashboard Cite

Granulocyte macrophage-colony stimulation factor (GM-CSF), which is a haematopoietic cytokine generated by activated T lymphocytes and macrophages during infection, was investigated for its effects on human neutrophil-mediated killing of asexual blood forms of Plasmodium falciparum. Pretreatment of neutrophils with human recombinant-GM-CSF markedly increased the parasite killing (measured by a radiometric assay), in the presence of normal serum (containing complement), immune serum (IS), purified IgG (from IS) or heat inactivated IS. GM-CSF pretreatment also enhanced phagocytosis of the parasite by neutrophils and the expression of CR3, Fc gamma RII and Fc gamma RIII receptors. Treatment of neutrophils with a combination of GM-CSF and TNF resulted in a synergistic increase in phagocytosis and killing of the parasite. The findings suggest that GM-CSF is likely to form part of the cytokine network responsible for regulating the antiparasitic activity of the neutrophil in malaria.

show abstract

A synthetic tumor necrosis factor-alpha agonist peptide enhances human polymorphonuclear leukocyte-mediated killing of Plasmodium falciparum in vitro and suppresses Plasmodium chabaudi infection in mice.

Cited by 23 publications

References 35 publications

Tumor Necrosis Factor in Falciparum Malaria

Tumor Necrosis Factor in Falciparum Malaria

A defunctioning polymorphism in FCGR2B is associated with protection against malaria but susceptibility to systemic lupus erythematosus

GM‐CSF‐induced priming of human neutrophils for enhanced phagocytosis and killing of asexual blood stages of Plasmodium falciparum: synergistic effects of GM‐CSF and TNF

Contact Info

Product

Resources

About