Acta Tropica 113 (2010) 263–268
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Acta Tropica
journal homepage: www.elsevier.com/locate/actatropica
A preliminary study on pro- and anti-inflammatory cytokine profiles in
Plasmodium vivax malaria patients from central zone of India
Vidhan Jain
a,1
, Puspendra P. Singh
a,1
, Nipun Silawat
a
, Rakesh Patel
a
, Ajay Saxena
a
,
Praveen K. Bharti
a
, Manmohan Shukla
a
, Sukla Biswas
b
, Neeru Singh
a,c,∗
a
National Institute of Malaria Research, FS-Jabalpur, MP, India
b
National Institute of Malaria Research, 22 Sham Nath Marg, Delhi 110054, India
c
Regional Medical Research Centre for Tribals & National Institute of Malaria Research, FS-Jabalpur, Nagpur Road, Garha, Jabalpur, MP, India
article info
Article history:
Received 16 January 2009
Received in revised form
11 November 2009
Accepted 24 November 2009
Available online 1 December 2009
Keywords:
Malaria
Plasmodium vivax
Cytokines
ELISA
abstract
The aim of this preliminary study was to investigate the plasma cytokine profiles in a group of patients
suffering from Plasmodium vivax malaria during the peak of its transmission season. Plasma samples
of 173 P. vivax patients and 34 healthy individuals were analyzed for IFN-, TNF-, IL-10 and IP-10
levels by ELISA. Levels of both pro- and anti-inflammatory cytokines were significantly higher in P. vivax
patients compared to controls. Children with P. vivax infection had significantly higher levels of IFN-
than adults (P = 0.017). Asexual parasitaemia versus TNF- (r = -0.31, P = 0.01), IL-10 (r = -0.30, P = 0.015)
and gametocytaemia versus IFN- (r = -0.26; P = 0.034) levels showed significant negative correlation in
children compared to adults. The median concentrations of IFN- (P = 0.001), IL-10 (P = 0.032) and IP-10
(P ≤ 0.05) were higher in children reported with chills and rigors, whereas in adults only IFN- levels was
higher (P < 0.0001). The median plasma concentrations of IFN- (P = 0.02), IL-10 (P < 0.0001) and IP-10
(P = 0.068) were higher in patients with mild anaemia compared to non-anaemic patients. The results
indicated that both pro- and anti-inflammatory cytokine responses are associated with clinical signs of
mild anaemia and paroxysm during symptomatic P. vivax malaria in Central India.
© 2009 Elsevier B.V. All rights reserved.
1. Introduction
Malaria is the major cause of morbidity and mortality in
many tropics and subtropics (especially of Asia and Latin Amer-
ica) including India where ∼52% of the malaria infections are
caused by Plasmodium vivax followed by Plasmodium falciparum
(www.nvbdcp.gov.in). This study has been carried out in a cen-
tral part of India, where both the species of Plasmodium, i.e.,
P. vivax and P. falciparum are prevalent in all age groups, espe-
cially in older children (Singh et al., 2000). In this area, malaria
is highly seasonal; P. vivax cases are common during dry season
(February–June), whereas P. falciparum cases are available during
post-monsoon periods from July to January. Though most of the P.
vivax infections are uncomplicated and rarely fatal, this can lead to
debilitating illness (Mendis and Carter, 1992). The problem is fur-
ther compounded by the development of chloroquine resistance
against P. vivax (Dua et al., 1996; Singh, 2000). Severe and com-
∗
Corresponding author at: Regional Medical Research Centre for Tribals, & OIC,
National Institute of Malaria Research, FS-Jabalpur, Nagpur Road, Garha, Jabalpur
482003, MP, India. Tel.: +91 7612371279; fax: +91 7612672900.
E-mail address: neeru.singh@gmail.com (N. Singh).
1
These authors contributed equally in this study.
plicated forms of P. vivax malaria causing cerebral malaria, renal
failure, severe anaemia, jaundice and even death in some patients
are reported from Western India (Kochar et al., 2005, 2007).
Like P. falciparum, P. vivax also induces specific immune
responses in host; as a result cytokines are released causing
activation of macrophages, T-lymphocytes, natural killer cells, neu-
trophils to combat the infection. Cytokine profile (TH1/TH2) unveils
the immune response in the disease. In Plasmodial infections, the
balance between pro- and anti-inflammatory cytokines determines
the level of anaemia, parasite load, degree of pyrexia, clinical sever-
ity and outcome of infection (Brown et al., 1991; Newton and
Krishna, 1998; Jason et al., 2001; Dodoo et al., 2002).
Although role of TNF-, IFN-, IL-10 and IL-4 has been investi-
gated in P. falciparum infection and related pathogenesis of malaria
information regarding P. vivax malaria and cytokines are relatively
rare (Yeom et al., 2003; Seoh et al., 2003; Karunaweera et al.,
1992a,b). Almost no information is available from central part of
India, where P. vivax malaria is highly prevalent and seasonal (Singh
et al., 2000, 2006). Thus exploring P. vivax cytokine profile would
be useful as it reveals the immune response mechanism of the host
against the parasite.
The aim of this preliminary study was to test the hypothesis that
cytokines may play an important role in immunopathogenesis of
P. vivax associated clinico-pathological features such as anaemia
0001-706X/$ – see front matter © 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.actatropica.2009.11.009