CLINICAL AND VACCINE IMMUNOLOGY, Sept. 2008, p. 1456–1460 Vol. 15, No. 9
1556-6811/08/$08.00
0 doi:10.1128/CVI.00506-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Levels of Soluble CD163 and Severity of Malaria in Children in Ghana

Kwadwo A. Kusi,1,4† Ben A. Gyan,1* Bamenla Q. Goka,2 Daniel Dodoo,1 George Obeng-Adjei,2
Marita Troye-Blomberg,3 Bartholomew D. Akanmori,1 and Jonathan P. Adjimani4
Immunology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana,
Legon, Ghana1; Department of Child Health, University of Ghana Medical School, College of Health Sciences,
Korle-Bu Teaching Hospital, Accra, Ghana2; Department of Immunology, Wenner-Gren Institute,
Stockholm University, Stockholm, Sweden3; and Department of
Biochemistry, University of Ghana, Legon, Ghana4
Received 10 December 2007/Returned for modification 4 February 2008/Accepted 4 July 2008
CD163 is an acute-phase-regulated monocyte/macrophage membrane receptor expressed late in inflamma-
tion. It is involved in the haptoglobin-mediated removal of free hemoglobin from plasma, has been identified
as a naturally soluble plasma glycoprotein with potential anti-inflammatory properties, and is possibly linked
to an individual’s haptoglobin phenotype. High levels of soluble CD163 (sCD163) in a malaria episode may
therefore downregulate inflammation and curb disease severity. In order to verify this, the relationships
between sCD163 levels, malaria severity, and selected inflammatory mediators (tumor necrosis factor alpha
[TNF-
], interleukin-6 [IL-6], and IL-10) were assessed by enzyme-linked immunosorbent assay using plasma
samples obtained from pediatric malaria patients with uncomplicated malaria (UM [n  38]), cerebral
malaria (CM [n  52]), and severe malarial anemia (SA [n  55]) during two consecutive malaria transmis-
sion seasons (2002 and 2003). Median sCD163 levels were higher in UM (11.9 g/ml) patients than in SA (7.7
g/ml; P  0.010) and CM (8.0 g/ml; P  0.031) patients. Levels of sCD163 were also higher in all patient
groups than in a group of 81 age-matched healthy controls. The higher sCD163/TNF-
 ratio in UM patients,
coupled with the fact that sCD163 levels correlated with TNF-
 levels in UM patients but not in CM and SA
patients, suggests inflammatory dysregulation in the complicated cases. The study showed that sCD163 levels
are elevated during acute malaria. High sCD163 levels in UM patients may be due to the induction of
higher-level anti-inflammatory responses, enabling them to avoid disease complications. It is also possible that
UM patients simply lost their CD163 receptors from macrophages in inflammatory sites while complicated-
malaria patients still had their receptors attached to activated macrophages, reflecting ongoing and higher-
level inflammation associated with complicated malaria.
CD163 is a group B cysteine-rich scavenger membrane re- ators. CD163 is, for example, known to upregulate the expression
ceptor that is expressed by cells of the monocytic lineage and of interleukin-10 (IL-10) as well as heme oxygenase-1 (HO-1),
is involved in the macrophage recognition and uptake of hap- both of which exert anti-inflammatory effects during the resolu-
toglobin-hemoglobin (Hp-Hb) complexes (11). CD163 is also tion phase of inflammation (14, 19, 24). Moreover, the expression
believed to bind free Hb, though less efficiently than the com- of membrane-bound CD163 is tightly regulated by inflammatory
plex, after total Hp depletion during severe hemolytic episodes mediators (9, 25). The soluble receptor is, however, known to
(20). Recent studies of rodents have also identified CD163 as have direct anti-inflammatory properties. sCD163 has been iden-
an adhesion receptor for erythroblasts, suggesting a possible tified as an anti-inflammatory mediator that inhibits phorbol es-
role for the membrane receptor (5). ter-induced human T-lymphocyte activation, resulting in the
CD163 can also be shed as a soluble plasma glycoprotein by attenuation of the immune response to the phorbol ester (10).
mechanisms not yet completely understood, though TIMP3- Macrophages that express the CD163 receptor generally ap-
sensitive metalloproteinases have been implicated in this shed- pear late in inflammation (7, 25); hence, CD163 shedding is
ding process (4, 15). Shedding has also recently been linked to
oxidative stress that results from inflammation or from induc- expected to occur during the late phase of the inflammatory
tion by 8-iso-prostaglandin F2 (22). cascade. The soluble receptor will then contribute to down-
Both membrane-bound CD163 and soluble CD163 (sCD163) regulating proinflammatory cytokine release in order to re-
have been identified as promoters of anti-inflammation. The store a balance in the levels of pro- and anti-inflammatory
membrane-bound receptor indirectly contributes to anti-inflam- mediators. During malaria infections, the balance between
mation by regulating the expression of other inflammatory medi- pro- and anti-inflammatory cytokines is important in defining
the course of the disease, particularly between subjects with
complicated malaria and those with uncomplicated malaria
* Corresponding author. Mailing address: Immunology Depart- (UM) (1, 13, 18). Thus, patients with UM may be expected to
ment, Noguchi Memorial Institute for Medical Research, P.O. Box have higher levels of sCD163 than patients with complicated
LG581, University of Ghana, Legon, Ghana. Phone: 233-24-4726016. malaria. This study examined the relationship between plasma
Fax: 233-21-502182. E-mail: bgyan@noguchi.mimcom.net. levels of sCD163 and disease severity, as well as the plasma
† Present address: Parasitology Dept., Biomedical Primate Research
Centre, Rijswijk, The Netherlands. levels of tumor necrosis factor alpha (TNF-), interleukin-6

 Published ahead of print on 16 July 2008. (IL-6), and IL-10 in Ghanaian pediatric malaria patients.
1456
VOL. 15, 2008 SOLUBLE CD163 LEVELS AND SEVERITY OF MALARIA 1457
MATERIALS AND METHODS TABLE 1. Characteristics of patients with UM
Patients and sampling. This study was part of an ongoing study conducted at and complicated malaria
the Department of Child Health of the Korle-Bu Teaching Hospital, Ghana, and No. of a a Parasite density
the Noguchi Memorial Institute for Medical Research (NMIMR), Ghana. Disease patients Hb concn (g/dl) Age (yr) (103/l)a
Plasma samples (frozen at 80°C) obtained from complicated malaria and UM
patients between the ages of 0.5 and 12 years who reported for medical care at UM 38 9.5 (2.3–4.9) 4.0 (1.0–12.0) 70.1 (3.74–4,340.2)
b b c
the hospital between 2002 and 2003 were used in this study. Blood samples were SA 55 3.9 (8.1–12.2) 2.0 (0.5–9.0) 52.2 (2.75–567.3)
b b c
also taken from a group of healthy, age-matched controls recruited from schools CM 52 7.6 (5.1–12.7) 4.0 (0.5–12.0) 98.1 (2.61–1,872.4)
in communities in the vicinity of the hospital. The blood samples had earlier been a Values are reported as medians (minimum to maximum values).
examined for malaria parasites and Hb levels. The inclusion criteria for malaria b Values are significant at a P of 0.0001 compared to those for UM subjects
patients were as previously published (13), with some modifications: fever (one-way analysis of variance).
(37.5°C), measured within 24 h of admission; asexual parasitemia of 2,500 c Values are not significant at a P of 0.251 compared to those for UM subjects
parasites/l; and at least one other sign of malaria, such as vomiting, diarrhea, or (one-way analysis of variance).
malaise. Also, patients had to be sickling negative and bacteremia negative and
have no other disease. The subjects were divided into groups of patients with
cerebral malaria (CM), severe malarial anemia (SA), and UM as follows: CM
was defined by an unarousable coma (score of 3 on the Blantyre coma scale) Franklin, MA) were used. Purified rat anti-human antibody (2 g/ml; BD Bio-
and no other neurological manifestation; SA was defined by a blood hemoglobin sciences, San Jose, CA) was used as the capture antibody, recombinant human
concentration of 5 g/dl, full consciousness, and no other cause of anemia; and TNF- (twofold serial dilutions from 2,000 to 15 pg/ml; BD Biosciences, San
UM was defined as described for SA, except with the addition of an Hb con- Jose, CA) as the standard, and biotin-conjugated mouse anti-human TNF- (1
centration of 8 g/dl and no other complication of malaria. The study received g/ml; BD Biosciences, San Jose, CA) as the detection antibody. Streptavidin-
ethical approval from the Institutional Review Board of the Noguchi Memorial peroxidase (KPL, Gaithersburg, MD) was added at 0.125 g/ml (1/4,000 dilution
Institute for Medical Research and the Ethical Committee of the University of of the stock), and then the plates were washed 10 times before the substrate
Ghana Medical School. addition, color development, and optical density reading at 492/620 nm.
Parasitological and hematological measurements. The hematological param- Patient management. The treatment of malaria was carried out in accordance
eters, including Hb levels, total white blood cell (WBC) counts, total red blood with the existing institutional guidelines at the time. All patients with UM were
cell counts, and mean corpuscular volume, were measured with an automated treated with chloroquine at a total dose of 25 mg/kg body weight, given as single
hematological analyzer (model KX-21; Sysmex, Japan). Thick and thin blood daily doses over 3 days. In the case of treatment failure, the treatment was
films were stained with Giemsa stain and examined for malaria parasites, which changed to amodiaquine (10 mg/kg body weight per day as single daily doses for
were counted against 200 WBCs. Parasite densities were obtained by multiplying 3 days). Patients with severe malaria were treated with either amodiaquine syrup
the total WBC counts by the number of parasites in 200 WBCs. Sickling tests via a nasogastric tube at the same dosage as stated or intramuscular quinine
were done using the sodium metabisulfite test, and sickling-positive patients were sulfate (10 mg/kg body weight every 8 hours). The treatment with intramuscular
excluded from the study. quinine was changed to syrup at the same dosage when patients regained full
sCD163 measurement. Immulon 2 microtiter plates (Thermo Labsystems, consciousness or after 72 h (whichever was earlier) to complete a 7-day course.
Franklin, MA) were coated with polyclonal rabbit anti-CD163 immunoglobulin In addition, patients with Hb levels of 5g/dl received blood transfusions.
G (BD Biosciences, San Jose, CA) at 2 g/ml and incubated overnight at 4°C. Statistical analysis. The Mann-Whitney U test and a one-way analysis of
The plates were then washed four times with phosphate-buffered saline (PBS)– variance (SigmaStat 2.0; Jandel Scientific, San Rafael, CA) were used for all
Tween 20 (0.05%) and blocked with 150 l/well of 3% bovine serum albumin in comparisons. Dot plots and line graphs displaying sCD163 levels were created
PBS, pH 7.2 to 7.4, for an hour. Recombinant human CD163 standards (BD with GraphPad Prism version 4.0 (GraphPad Software, San Diego, CA). Corre-
Biosciences, San Jose, CA) diluted serially from 3,000 ng/ml to 1.37 ng/ml and lation and linear regression analyses were also performed with SPSS version 9.0
plasma samples diluted 1:100 in 1% bovine serum albumin-PBS were added in (SPSS, San Diego, CA). Differences with a P of 0.05 were considered statisti-
duplicate at 100 l/well and incubated for 90 min. After the wells were washed cally significant.
twice, 100 l/well of 1 g/ml mouse monoclonal anti-CD163 antibody (GHI/61)
([r]BD Biosciences, San Jose, CA) was added and incubated for 1 h. The plates
were washed four times, and 100 l/well of peroxidase-labeled goat anti-mouse RESULTS
immunoglobulin (Dako, Carpenteria, CA) was added to each plate and incu-
bated for 1 h. Finally, the plates were washed five times, and 100 l/well of Characteristics of patient groups. The objectives of this
substrate solution (0.4 mg/ml orthophenyldiamine in 0.025 M citrate, 0.05 M study were to compare the plasma levels of sCD163 in patients
phosphate buffer, pH 5.0, 0.012% H2O2) was added. After 30 min of color with UM with the levels in those with complicated pediatric
development, 50 l/well of stop solution (1 M H2SO4) was added and the optical malaria and to correlate sCD163 levels with the levels of the
density was read at 492 nm with a 620-nm reference wavelength using an enzyme- inflammatory mediators TNF-, IL-6, and IL-10. A total of 52
linked immunosorbent assay (ELISA) plate reader (Thermo Labsystems, Hel-
sinki, Finland). patients with CM (median age, 4.0 years), 55 with SA (median
Cytokine measurements. IL-6 and IL-10 were detected in plasma by ELISA age, 2.0 years), and 38 with UM (median age, 4.0 years) were
according to manufacturers’ protocols. Briefly, MaxiSorp microtiter plates included in this study. The median age of the patients in the SA
(Nunc, Roskilde, Denmark) were coated with 4 g/ml of the respective purified category was significantly lower than those of the other disease
rat anti-human antibodies (BD Biosciences, San Jose, CA) at 50 l/well and categories (P  0.001). Also, the levels of parasitemia were not
incubated overnight at 4°C. The plates were washed four times with PBS-Tween
20 (0.05%) and blocked with 150 l/well of 5% heat-inactivated fetal bovine statistically different (P  0.251) among the three study groups
serum (FBS) in PBS for 1 h at room temperature. After the plates were washed (Table 1).
twice, recombinant standards (threefold serial dilutions from 4,000 to 1.83 pg/ml; sCD163 levels in malaria patients and controls. The plasma
BD Biosciences, San Jose, CA) and undiluted serum samples were added at 50 levels of sCD163 were determined by sandwich ELISA, and
l/well and incubated on a shaker for 2 h at room temperature. After the plates Fig. 1 shows the median levels of sCD163 among the three
were washed four times, 1 g/ml biotinylated anti-human cytokine antibodies
(BD Biosciences, San Jose, CA) in 5% heat-inactivated FBS in PBS were added patient categories. The median level of sCD163 was signifi-
at 50 l/well and incubated at room temperature for 45 min. The plates were cantly higher in UM patients (11.9 g/ml; range, 1.5 to 76.6
washed five times, and 0.5 g/ml streptavidin-peroxidase (1/1,000 dilution of g/ml) than they were in CM patients (8.0 g/ml; range, 1.4 to
stock in 5% FBS in PBS; KPL, Gaithersburg, MD) was added at 50 l/well and 48.9 g/ml; P  0.031) and SA patients (7.7 g/ml; range, 0.94
incubated for 30 min at room temperature. The plates were then washed eight
times after the incubation period and developed with orthophenyldiamine sub- to 40.0 g/ml; P  0.01). Compared with patients in the com-
strate for 30 min, and then optical densities were read at 492/620 nm. bined SA and CM groups designated the complicated-malaria
For the TNF- ELISA, Immulon 2 microtiter plates (Thermo Labsystems, group, patients with UM still showed significantly higher
1458 KUSI ET AL. CLIN. VACCINE IMMUNOL.
FIG. 1. Levels of sCD163 in the three patient categories and healthy controls. The levels were determined by sandwich ELISA for 38 patients
with UM, 52 with CM, and 55 with SA, alongside 81 healthy controls (CNTRL). The horizontal lines represent the medians of the distributions.
sCD163 levels (P  0.007). Levels were, however, not signifi- to a 47-fold increase in plasma sCD163 levels. There were no
cantly different between patients with SA and CM. When the correlations or associations between sCD163 levels and those
median sCD163 level of a group of 81 age-matched healthy of IL-6 and IL-10 (data not shown).
controls (0.03 g/ml; range, 0.01 to 0.82 g/ml) was compared Since disease outcome to some extent depends on the bal-
with that of each of the three disease categories, the level was ance in the levels of pro- and anti-inflammatory mediators, the
significantly lower (P  0.0001) in the healthy control group in ratios of sCD163 to the measured cytokines were compared
all cases. between disease categories by the Mann-Whitney U test. Me-
To determine the possible changes in the levels of sCD163 dian sCD163/TNF- ratios were significantly higher in UM
during recovery from malaria, three patients designated A, B, patients (0.37; range, 0.02 to 3.38) than in SA patients (0.23;
and C whose plasma samples for day 3 and day 14 were avail- range, 0.01 to 2.67; P  0.014) but not in CM patients (0.32;
able were analyzed for their sCD163 levels. For patient A, the range, 0.03 to 2.15; P  0.132). The median ratios between CM
sCD163 level decreased from 7.0 g/ml on day 0 to 2.5 g/ml and SA patients were not statistically different (P  0.437). No
by day 3 and then decreased further to 1.6 g/ml on day 14. For such associations were found for ratios between sCD163 and
patient B, the level decreased from 8.6 g/ml on day 0 to 3.5 IL-6 or IL-10 (data not shown).
g/ml by day 3 but increased to 4.5 g/ml on day 14. Similarly, Correlation analysis between sCD163 and other clinical pa-
for patient C, the level decreased from 3.8 g/ml on day 0 to rameters showed a positive correlation (r  0.213; P  0.005)
1.5 g/ml on day 3 but increased to 3.0 g/ml on day 14. with Hb levels but not with parasitemia or age.
sCD163 and disease indicators in patients. The plasma con-
centrations of cytokines were compared with sCD163 levels, DISCUSSION
since CD163 expression is regulated by cytokines. A significant
positive correlation was observed between the levels of The results of this study reveal an elevation in sCD163 levels
sCD163 and TNF- (r  0.316; P  0.0001) for all disease in the plasma of both complicated malaria and UM cases
categories combined. When correlation analyses were done by compared to the levels in healthy Ghanaian children. The
disease categories, however, sCD163 levels correlated signifi- elevation of sCD163 levels in patients with diseases like rheu-
cantly with TNF- levels in UM patients (r  0.426; P  matoid arthritis and pneumonia has been described previously
0.0038) but not those in SA (r  0.116; P  0.199) or CM (r  (15, 16). The significantly higher levels of sCD163 in UM cases
0.178; P  0.109) patients (Fig. 2). A linear regression analysis compared to complicated-malaria cases may suggest a protec-
using combined data from all cases showed an association of tive role against malaria for the soluble form of the receptor
high levels of sCD163 with serum levels of TNF- (P  0.001). protein. The differences in sCD163 levels between UM and
Indeed, a unit increase in plasma TNF- levels corresponded complicated-malaria cases may be explained by one of two
VOL. 15, 2008 SOLUBLE CD163 LEVELS AND SEVERITY OF MALARIA 1459
FIG. 2. Correlation between plasma sCD163 levels and TNF levels in CM patients (A), SA patients (B), and UM patients (C). The P values
were obtained after a Pearson product correlation test.
phenomena: either higher anti-inflammatory responses were support to the reasoning that sCD163 may play an important
induced in UM patients, enabling them to avoid disease com- anti-inflammatory and/or immunoregulatory role in malaria
plications, or UM patients simply lost their CD163 receptors pathology (6, 8). Thus, it may be hypothesized that UM pa-
from macrophages in inflammatory sites, while the complicated- tients are better able to regulate inflammation due to proin-
malaria patients still had their receptors attached to activated flammatory cytokines such as TNF- by suppressing their pro-
macrophages, reflecting an ongoing and higher level of inflam- duction later during infection. That the anti-inflammatory
mation associated with complicated malaria. properties of sCD163 may be crucial in protecting against
In our study, sCD163 levels were generally high during acute complicated malaria and other inflammation-mediated condi-
infection but fell gradually during recovery. This is in agree- tions is also supported by the fact that the soluble receptor
ment with the general observation that sCD163 levels are usu- occurs in microgram quantities, unlike with many other inflam-
ally increased under the inflammatory conditions brought matory mediators, whose plasma levels are generally much
about by inflammation but fall gradually during recovery from lower.
inflammation and, in this study, after parasite clearance. The No associations were observed between sCD163 levels and
levels of sCD163 for patient A decreased further on day 14, but those of IL-6 or IL-10, though previous studies have reported
patients B and C recorded slight increases on the same day. that CD163 expression on monocytes/macrophages is induced
These differences in the variation patterns of sCD163 levels 14 by IL-6 and IL-10 (3, 21). Thus, it may be deduced that IL-6
days after treatment commenced may reflect a homeostatic and IL-10 have a bearing only on the membrane expression
adjustment in order to return to normal levels after recovery. and not on the process of sCD163 shedding. The single-point
These observations are nevertheless inconclusive, and the elu- measurements done in this study, however, make such an ar-
cidation of this finding would require a longitudinal study with gument inconclusive. These findings notwithstanding, it may be
a larger sample size. important to further investigate a possible role for TNF- in
There was a positive significant correlation between plasma the expression and/or shedding of CD163. Indeed, TNF- is
levels of sCD163 and those of TNF for UM patients but not for known to induce the hepatic synthesis of Hp (2), an acute-
SA and CM patients, as shown in Fig. 2. This may suggest an phase glycoprotein that regulates CD163 expression on mono-
attempt to counterbalance the effects of the high levels of the cytes/macrophages. Studies have shown that macrophages are
proinflammatory TNF by the anti-inflammatory sCD163 in heterogeneous in nature, and while one population is capable
UM patients, a situation which is absent in the severe-malaria of inducing the production of inflammatory mediators such as
(SA and CM) patients. Thus, in the complicated cases (SA and TNF-, another population of macrophages induces the pro-
CM), there is a dysregulation of inflammatory mediators. duction of anti-inflammatory mediators such as sCD163 (23).
Dysregulation of inflammatory mediators has been associ- It is therefore not unusual to have high levels of both media-
ated with disease severity in malaria (1) and other inflamma- tors in a disease situation, as our data show.
tory disease states (12). sCD163/TNF- ratios were also higher Levels of sCD163 also correlated positively with Hb levels
in UM patients than in CM and SA patients, suggesting the but not with parasitemia or age. Membrane-bound CD163 has
presence of relatively higher levels of the proinflammatory been recently identified as an important receptor in erythro-
cytokine TNF-, especially in SA patients. This also lends poiesis in rodents (5), and since the levels of sCD163 are a
1460 KUSI ET AL. CLIN. VACCINE IMMUNOL.
reflection of the expression level of the membrane-bound form 8. Graversen, J. H., M. Madsen, and S. K. Moestrup. 2002. CD163: a signal
(17), it may be predictably argued that the severe malaria receptor scavenging haptoglobin-hemoglobin complexes from plasma. Int.J. Biochem. Cell Biol. 34:309–314.
patients (SA and CM patients) who had relatively low levels of 9. Hogger, P., U. Erpenstein, P. Rohdewald, and C. Sorg. 1998. Biochemical
sCD163 would also have low Hb levels due to some impair- characterization of a glucocorticoid-induced membrane protein (RM3/1) in
ment or a decreased rate of their erythropoietic process. There human monocytes and its application as model system for ranking glucocor-ticoid potency. Pharm. Res. 15:300–306.
is, however, the possibility that this erythropoietic function of 10. Hogger, P., and C. Sorg. 2001. Soluble CD163 inhibits phorbol ester-induced
CD163 may not be applicable to humans. lymphocyte proliferation. Biochem. Biophys. Res. Commun. 288:841–843.
11. Kristiansen, M., J. H. Graversen, C. Jacobsen, O. Sonne, H. J. Hoffman,
In conclusion, sCD163 levels are generally increased during S. K. Law, and S. K. Moestrup. 2001. Identification of the haemoglobin
a malaria infection. There are, however, highly elevated levels scavenger receptor. Nature 409:198–201.
of sCD163 in the plasma of UM patients relative to levels in 12. Kulmatycki, K. M., and F. Jamali. 2005. Drug disease interactions: role ofinflammatory mediators in disease and variability in drug response. J. Pharm.
complicated-malaria patients, and these high levels may confer Pharm. Sci. 8:602–625.
relative protection against complicated malaria by regulating 13. Kurtzhals, J. A. L., V. Adabayeri, B. Q. Goka, B. D. Akanmori, J. O. Oliver-
inflammation. Additionally, the correlation of sCD163 levels Commey, F. K. Nkrumah, C. Behr, and L. Hviid. 1998. Low plasma concen-trations of interleukin 10 in severe malarial anaemia compared with cerebral
with levels of TNF-, a key inflammatory mediator in the and uncomplicated malaria. Lancet 351:1768–1772.
pathogenesis of malaria, taken together with the timely pro- 14. Lee, T.-S., and L.-Y. Chau. 2002. Heme oxygenase-1 mediates the anti-
inflammatory effect of interleukin-10 in mice. Nat. Med. 8:240–246.
duction of sCD163 late during the inflammatory cascade, sug- 15. Matsushita, N., M. Kashiwagi, R. Wait, R. Nagayoshi, M. Nakamura, T.
gests a key role for sCD163 in the complex network of inflam- Matsuda, P. Hogger, P. M. Guyre, H. Nagase, and T. Matsuyama. 2002.
matory mediation and/or regulation of the pathogenesis of Elevated levels of soluble CD163 in sera and body fluids from rheumatoid
arthritis patients and inhibition of the shedding of CD163 by TIMP-3. Clin.
clinical malaria. sCD163 may therefore be a potential candi- Exp. Immunol. 130:156–161.
date for anti-inflammatory therapy not only for malaria but 16. Moller, H. J., H. Aerts, H. Gronbaek, N. A. Peterslund, P. Hyltoft-Petersen,
also for other inflammation-mediated diseases and conditions. N. Hornung, L. Rejnmark, E. Jabbarpour, and S. K. Moestrup. 2002. Sol-uble CD163: a marker molecule for monocyte/macrophage activity in dis-
ease. Scand. J. Clin. Lab. Investig. 237:29–33.
ACKNOWLEDGMENTS 17. Moller, H. J., N. A. Peterslund, J. H. Graversen, and S. K. Moestrup. 2002.
Identification of the haemoglobin scavenger receptor/CD163 as a natural
This study received financial support from a WHO/TDR/MIM Re- soluble protein in plasma. Blood 99:378–380.
Entry grant (A-10938). 18. Othoro, C., A. A. Lal, B. Nahlen, D. Koech, A. S. Orago, and V. Udhayakumar.
The CD163 standard protein was gracefully provided by Soren K. 1999. A low interleukin-10/tumor necrosis factor alpha ratio is associated with
Moestrup of the Department of Medical Biochemistry, University of malarial anaemia in children residing in a holoendemic malaria region in west-
Aarhus, Denmark. The members of staff of Immunology Department, ern Kenya. J. Infect. Dis. 179:279–282.
NMIMR, are thanked for their excellent technical assistance. 19. Philippidis, P., J. C. Mason, B. J. Evans, I. Nadra, K. M. Taylor, D. O.Haskard, and R. C. Landis. 2004. Hemoglobin scavenger receptor CD163
mediates interleukin-10 release and heme oxygenase-1 synthesis: antiinflam-
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