Association between Elevated TNF-α Levels and

Severe Malaria

Khalid Abdelsamea Mohamedahmed1,2

1 Department of Hematology and Immunohematology, Faculty of Medical Laboratory Sciences, University of Gezira, Wad Medani,

Sudan

2 Department of Hematology and Immunology, Faculty of Medical Laboratory Sciences, University of Gezira, Wad Medani, Sudan

GMJ.2023;12:e2927

www.gmj.ir

 Correspondence to:

Khalid Abdelsamea Mohamedahmed, Department of

Hematology and Department of Immunology, Faculty

of Medical Laboratory Science, University of Gezira,

Wad Medani, Sudan

Telephone Number: +249114660424

Email Address: khalid.gu89@gmail.com

Received 2023-01-01

Revised 2023-03-04

Accepted 2023-03-05

Dear Editor,

Tumor necrosis factor-alpha (TNF-α) is

predominantly produced by γδ T cells and

CD14+ monocytes during immune responses

to malaria and helps in the control of parasite-

mia. TNF-α and interferon-gamma (IFN-γ)

act synergistically to optimize nitric oxide

production which in turn leads to parasite kill-

ing. Also, TNF-α enhances human neutrophil

killing of the plasmodium parasite [1].

TNF-α is play important role in the patho-

genesis of multiple inammatory disorders,

autoimmune diseases, and infectious diseases

including malaria [2, 3].

At low levels, TNF-α is believed to augment

parasite killing by macrophage activation and

subsequent release of cytokines, whereas high

TNF-α level has been associated with severe

manifestations. Individual variation in TNF-α

production mainly by macrophages and natu-

ral killer (NK) cells is likely to inuence se-

vere disease manifestation [2].

Severe malarial infection is associated with

the rupture of parasitized red blood cells re-

leasing malaria pigment and other soluble

antigens and toxins that stimulate the over-

production of TNF-α in human monocytes

and may also stimulate intense T helper type

1-like response locally, in tissues of vital or-

gans which result in upregulation of expres-

sion of endothelial adhesion molecules such

as intracellular adhesion molecule-1 (ICAM-

1) or other adhesion molecules.

This in turn leads to increased and enhanced

parasite adherence and sequestration of para-

sitized red cells that leads to subsequent mi-

crovascular obstruction, decreasing oxygen

delivery, and/or possibly the release of nitric

oxide (NO) from the endothelium which may

ultimately contribute to the pathogenesis [4].

Also, elevated TNF-α levels stimulated

phagocytosis and thereby enhanced clearance

of parasitized erythrocytes but the prolonged

response was associated with severe disease

syndromes.

TNF-α has been shown to increase the severi-

ty of inammation by inducing cyclooxygen-

ase-2 (COX-2) and subsequently generating

eector molecules, such as prostaglandins.

Many of the signs and symptoms and compli-

cations associated with malaria be linked to

TNF-α [4, 5].

TNF-α is considered to be important for par-

asite destruction and elimination, as well as

in the development of fever and other clini-

cal symptoms, and it also contributes to the

development of severe malaria disease [6].

TNF-α could aect the outcome of malaria in

several ways.

TNF-α promotes fever, which may suppress

parasite growth, and it also induces the ex-

pression of adhesion molecules and proin-

ammatory molecules [7]. Lethal cerebral

malaria (CM) has been associated with a high

level of TNF-α in serum [7].

The TNF-α overproduction in malaria can

contribute to reduced red cell production and

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Mohamedahmed kh, et al. TNF-α Levels and Severe Malaria

2GMJ.2023;12:e2927

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anemia through suppression of bone marrow

erythropoiesis and dyserythropoiesis [1, 8].

The overproduction of TNF-α could be asso-

ciated with more rapid resolution of fever and

parasite clearance but predisposes to severe

pathology of disease [9].

Severe malaria is associated with several

genes; including TNF-α gene polymorphisms.

TNF-α is thought to be a critical factor in ma-

laria pathogenesis, the control of parasitemia,

and increased susceptibility to severe malaria

[2, 10].

High TNF-α plasma levels have been asso-

ciated with increased susceptibility to severe

malaria [2, 10]. The variation in the TNF-α

gene phenotypes related to malaria infection

and severe disease [10].

In conclusion, Tumor necrosis factor (TNF-α)

is a common proinammatory cytokine. It

plays a central role in malaria pathogenicity

either in the cure or complication of malaria.

Their high level is associated with the severe

outcome of malaria. [GMJ.2023;12:e2927]

DOI:10.31661/gmj.v12i0.2927

Conict of Interest

The author has declared that no Conict of In-

terest exist.

Keywords

TNF-α; Severe Malaria; Proinammatory Cy-

tokine

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