Association of high plasma TNF-alpha levels and TNF-alpha/IL-10 ratios with TNF2 allele in severe<i>P. falciparum</i>malaria patients in Sri Lanka

Perera, M; Herath, Nimali; Pathirana, Sisira; Phone-Kyaw, M.; Alles, H. K.; Mendis, Kamini; Premawansa, Sunil; Handunnetti, Shiroma

doi:10.1179/2047773212y.0000000069

Cited by 38 publications

(32 citation statements)

References 43 publications

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“…Furthermore, Hz induces production of M2b‐specific cytokines—TNF‐α, IL‐1β, and IL‐6 in human MO. These data corroborate with reports demonstrating the presence of inflammatory cytokines IL‐1β, TNF‐α, and IL‐6 along with high level of anti‐inflammatory IL‐10 in plasma of malaria patients (Perera et al., ; Weinberg et al., ).…”

Section: Discussionsupporting

confidence: 91%

Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin

et al. 2018

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Plasmodium falciparum malaria is the most severe form of malaria with several complications. The malaria pigment-hemozoin (Hz) is associated with severe anemia, cytokine dysfunction, and immunosuppression, thus making it an interesting target for developing new strategies for antimalarial therapy. Monocytes (MO) in circulation actively ingest Hz released by Plasmodium parasites and secrete pro- and anti-inflammatory cytokines. M1 and M2 types represent the two major forms of MO/macrophages (MQ) with distinct phenotypes and opposing functions. Imbalance in the polarization of these types is reported in many infectious diseases. Though the association of Hz with immunosuppression is well documented, its role in activation of MO in context of M1/M2 phenotypes remains to be addressed. We report here that natural Hz drives human MO toward M2-like phenotype as evidenced by the expression of M2 signature markers. Hz-fed MO showed elevated transcript and secreted level of IL-10, CCL17, CCL1, expression of mannose-binding lectin receptor (CD206), and arginase activity. Hz attenuated HLA-DR expression, nitric oxide, and reactive oxygen species production, which are the features of M1 phenotype. Our data also implicate the involvement of p38 MAPK, PI3K/AKT, and NF-κB signaling pathways in skewing of Hz-fed MO toward M2-like type and suppression of mitogen-stimulated lymphocyte proliferation. Importantly, antimalarial drugs-chloroquine and artemisinin-partially reversed activation of Hz-induced MO toward M2-like phenotype. Considering the limitations in the current therapeutic options for malaria, we propose that these drugs may be re-examined for their potential as immunomodulators and candidates for adjunctive treatment in malaria.

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Section: Discussionsupporting

confidence: 91%

Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin

et al. 2018

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“…Our results also indicate that subjects carrying the A allele of TNFA (rs1800629) A/G had a lower risk of developing active HAT ( Table 2 ) or a latent infection ( Table 4 ), suggesting the possibility of a protective effect. This SNP is also known as the TNF -308 SNP and the minor A allele is associated with higher plasma levels of TNFA [ 24 ]. In a previous study in Côte d’Ivoire, Courtin et al .…”

Section: Discussionmentioning

confidence: 99%

Candidate genes-based investigation of susceptibility to Human African Trypanosomiasis in Côte d’Ivoire

et al. 2017

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Human African Trypanosomiasis (HAT) or sleeping sickness is a Neglected Tropical Disease. Long regarded as an invariably fatal disease, there is increasing evidence that infection by T. b. gambiense can result in a wide range of clinical outcomes, including latent infections, which are long lasting infections with no parasites detectable by microscopy. The determinants of this clinical diversity are not well understood but could be due in part to parasite or host genetic diversity in multiple genes, or their interactions. A candidate gene association study was conducted in Côte d’Ivoire using a case-control design which included a total of 233 subjects (100 active HAT cases, 100 controls and 33 latent infections). All three possible pairwise comparisons between the three phenotypes were tested using 96 SNPs in16 candidate genes (IL1, IL4, IL4R, IL6, IL8, IL10, IL12, IL12R, TNFA, INFG, MIF, APOL1, HPR, CFH, HLA-A and HLA-G). Data from 77 SNPs passed quality control. There were suggestive associations at three loci in IL6 and TNFA in the comparison between active cases and controls, one SNP in each of APOL1, MIF and IL6 in the comparison between latent infections and active cases and seven SNP in IL4, HLA-G and TNFA between latent infections and controls. No associations remained significant after Bonferroni correction, but the Benjamini Hochberg false discovery rate test indicated that there were strong probabilities that at least some of the associations were genuine. The excess of associations with latent infections despite the small number of samples available suggests that these subjects form a distinct genetic cluster different from active HAT cases and controls, although no clustering by phenotype was observed by principle component analysis. This underlines the complexity of the interactions existing between host genetic polymorphisms and parasite diversity.

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“…There has been no previous report on the antipyretic activity of the ethanol extract of the plant and this has prompt the evaluation of the plant for its antipyretic activity. Malaria is known to induce high body temperature in humans[ 30 ], and low temperature in rodent mice[ 31 ]. Using the two models of malaria treatment, it was shown that the extract displayed antipyretic activity at all the models by raising the body temperature in the malaria-infected mice.…”

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confidence: 99%

In vivo antimalarial activities of russelia equisetiformis in plasmodium berghei infected mice

Ojurongbe¹,

Ojo²,

Adefokun³

et al. 2015

Indian J Pharm Sci

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The rising problem of resistance to most commonly used antimalarials remains a major challenge in the control of malaria suggesting the need for new antimalarial agents. This work explores the antiplasmodial potential of ethanol extract of Russelia equisetiformis in chloroquine Plasmodium berghei infected mice. Swiss albino mice were intraperitoneally infected with chloroquine-resistant P. berghei (ANKA). Experimental mice were treated for four days consecutively with graded doses of plant extracts and standard antimalarial drugs (artesunate and chloroquine) at a dose of 10 mg/kg body weight used as control. The extract showed a dose-dependent activity in the chemosuppression of P. berghei parasites by 31.6, 44.7, 48.4 and 86.5% at doses of 100, 200, 400 and 800 mg/kg, while chloroquine (10 mg/kg) and artesunate produced 59.4 and 68.4%, respectively. The extract showed a significant decrease in parasitaemia (P<0.05). The level of parasitemia and decrease in weight in all the treated groups was significantly lower (P<0.05) compared with the infected but untreated mice. The plant extract was devoid of toxicity at the highest dose tested (5000 mg/kg). The study concluded that the ethanol extract of R. equisetiformis possesses antimalarial effect, which supports the folk medicine claim of its use in the treatment of malaria.

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Association of high plasma TNF-alpha levels and TNF-alpha/IL-10 ratios with TNF2 allele in severeP. falciparummalaria patients in Sri Lanka

Cited by 38 publications

References 43 publications

Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin

Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin

Candidate genes-based investigation of susceptibility to Human African Trypanosomiasis in Côte d’Ivoire

In vivo antimalarial activities of russelia equisetiformis in plasmodium berghei infected mice

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