Clinical Immunology 116 (2005) 271 – 278

www.elsevier.com/locate/yclim

Relationship between the clinical heterogeneity of neurocysticercosis and

the immune-inflammatory profiles
Anahı́ Chavarrı́aa, Agnes Fleuryb, Esperanza Garcı́ab, Carlos Márquezb,
Gladis Fragosoa, Edda Sciuttoa,*
a
Departamento de Inmunologı́a, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México,
UNAM, AP70228, México D.F. 04510, México
b
Instituto Nacional de Neurologı́a y Neurocirugı́a, Insurgentes Sur 3877, México D.F. 14269, México

Received 25 October 2004; accepted with revision 13 April 2005

Available online 2 June 2005

Abstract

Human neurocysticercosis is caused by the establishment of Taenia solium cysticerci in the central nervous system. Neurocysticercosis
may be asymptomatic or manifested by non-specific mild to severe neurological symptoms. Host factors may be involved in this
heterogeneous clinical picture. An immune-inflammatory profile that underlies neurocysticercosis presentation was determined in 45
cerebral spinal fluid (CSF), from clinical and radiologically characterized neurocysticercosis patients, measuring specific IgG subclasses
and cytokines. Severity related with increased cellularity in the CSF which was characterized by increased levels of IgG subclasses,
IL6/IL5/IL10, proteins, and eosinophils. Multiple neurocysticercosis showed higher levels of IL5/IL6 than single neurocysticercosis.
Women presented increased IL6/IL5/IL10 levels pointing out immunological differences due to gender. Severe symptomatology was
found when cysticerci were located intraventricular or in the subarachnoid space of the base, inducing an exacerbated response in the
CSF. These results constitute an integrative insight to understand the immune-inflammatory response that underlies symptomatic
neurocysticercosis.
D 2005 Elsevier Inc. All rights reserved.

Keywords: Taenia solium; Neurocysticercosis; CNS; Inflammation; Immunological profiles

Introduction In Mexico, it is the cause of 11% of neurological consulta-

Different expression profiles of cytokines and antibodies
associate with different disease status either of autoimmune,
traumatic, or infectious etiologies, in which the immune-
inflammatory response is closely related to symptomatology
and severity [1,2]. In the human central nervous system
(CNS), the local immune response induced by infections has
been poorly studied because of the difficulties to obtain
biological samples from well-characterized patients. This is
the case of neurocysticercosis (NC), a frequent and serious
parasitic disease of the CNS, caused by Taenia solium larvae.
* Corresponding author. Fax: +1 52 5556223369.
E-mail address: edda@servidor.unam.mx (E. Sciutto).
1521-6616/$ - see front matter D 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.clim.2005.04.008
tions [3], 25% of craniotomies [4], and the first cause of adult
onset epilepsy [5,6]. NC is a pleomorphic neurological
disease that presents a significant heterogeneity clinically and
radiologically. Indeed, NC can be completely asymptomatic
[7 – 9] or be manifested by a variety of non-specific
symptoms: headache, epilepsy, dementia, depression, and
even intracranial hypertension. The causes that underlie this
heterogeneity are not completely understood, although it is
speculated that host, parasite, and/or exposure factors are
involved [8,10 –13].
Differences in NC severity due to host immunological
factors have been barely explored. To begin approaching
this issue, we carried out a correlation study in which the
immunological profiles were matched to the clinical
categories of the disease. The effects of gender and age
272 A. Chavarrı́a et al. / Clinical Immunology 116 (2005) 271 – 278
were also considered because previous studies showed that
women display increased inflammatory CSF cellularity and
age was related to increased number of vesicular cysts
[13,14].
We previously proposed that different clinical NC
phenotypes (asymptomatic or mild to severe NC) might
be related to specific immune-inflammatory profiles. In a
previous study, the immunological profile related to
asymptomatic NC cases was characterized by increments
in the concentration of IL4, IL5, and IL13 in supernatants
of peripheral mononuclear cells after specific antigenic
stimulation and increased specific IgG4 levels in plasma
[9]. Thus, it seems that a TH2 profile promotes a silent
resolution of the NC infection. In this study, we explored if
an exacerbated immune-inflammatory profile relates with
the heterogeneity of the NC clinical presentation in well-
characterized symptomatic patients.
Materials and methods
Patients
The 45 patients included in this study were attended at
the Instituto Nacional de Neurologı́a y Neurocirugı́a
(INNN) in Mexico City and had never been treated for
NC before. INNN only admits patients older than 15 years
of age. Available CSF of these untreated patients was
included in the study that lasted from 2001 to 2003. Age
and gender data were collected from each patient.
Characterization of the disease
NC diagnosis was based on computed tomography (CT)
and magnetic resonance imaging (MRI) before receiving
specific treatment. Parasite stage was determined based on
the CT and/or MRI image: (1) vesicular (the parasite is
viable, a cerebrospinal fluid-like signal within a cyst is
seen); (2) colloidal (the cyst fluid is turbid, there is an
intense inflammatory reaction in the surrounding brain
parenchyma); (3) calcified (the parasite debris appear as a
mineralized granuloma).
From radiological studies of each NC case, the
following information was collected: number of lesions
(single vs. multiple), stage of cysticerci [vesicular,
colloidal, calcified, or mixed (colloidal and vesicular)
forms] and CNS location [subarachnoid space of the base
(SA base) or of the sulci (SA sulci), parenchymal, or
intraventricular].
CSF cellularity, content of proteins, and the presence of
eosinophils was recorded. CSF was considered inflamma-
tory when the number of cells exceeded 5/ml. High CSF
inflammation was considered when cells exceeded 15/ml,
three times the normal value.
The severity of symptoms associated with the disease
was established by clinical examination of the patients by
two neurologists. Based on symptomatology, patients were
grouped in three classes: (1) Mild: headache or no
symptoms; (2) Moderate: focal deficits and/or seizures; and
(3) Severe: intracranial hypertension (defined by presence of
headache, nausea, vomiting, and papilledema).
Immune-inflammatory profile
The following features were measured in the CSF to
define an immune-inflammatory profile related to NC: T.
solium specific anti-cysticercal IgG subclasses (IgG1,
IgG2, IgG3, IgG4) and IgE antibodies, TH1 (IL12, IFNg),
TH2 (IL4, IL5, IL10), and inflammatory (IL1h, IL6)
cytokines.
Cytokine titration
Sandwich ELISAs were performed in 96-well, flat-
bottom microtiter plates (Nunc-Immuno Plate Maxisorp,
Rosekilde, Denmark). Microplates were coated for 18 h at
4-C with the capture antibody (BD Pharmingen, San
Diego, CA for IL1h, IL4, IL5, IL6, IL10, IL12, and
INFg), washed three times with PBS-Tween 20 (0.05%),
blocked for 30 min at room temperature with PBS-BSA
2%, washed three times. Thereafter, plates were incubated
for 18 h at 4-C with cytokine standards and CSF diluted
1:3 with PBS-Tween 20 (0.05%) –BSA 0.5%, washed
three times, and incubated with the detection antibody
(BD Pharmingen for IL1h, IL4, IL5, IL6, IL10, IL12, and
INFg) for 2 h at room temperature. Bound detection
antibodies were detected using streptavidin –phosphatase
conjugate (1:3000; Zymed Laboratories, San Francisco,
CA) and p-nitrophenyl phosphate (Sigma, St. Louis, MO)
as substrate. Optical density (OD) readings were per-
formed at 405 nm, after 30 and 60 min of incubation. All
assays were performed in duplicate and their sensitivity
was 9.4 pg/ml for all cytokines.
IgG subclasses and IgE antibody detection by ELISA
CSF antibody levels were measured by indirect
ELISA. T. solium cyst fluid (1 Ag/100 Al/well) was
incubated 18 h at 4-C in carbonate buffer pH 9.5. The
wells were washed, incubated with CSF diluted 1:10 for 1
h at 37-C. Bound immunoglobulins were developed using
rabbit anti-human IgG1, IgG2, IgG3, or IgG4 coupled to
biotin (1:1000; Zymed Laboratories, San Francisco CA),
streptavidin – alkaline phosphatase conjugate (1:3000;
Zymed) and p-nitrophenyl phosphate (Sigma) as substrate.
Plates were read at 405 nm following 30 min of
incubation. All assays were performed in duplicate.
Statistical analysis
Data were processed in Excel 7.0 (Microsoft) and Spss
10.0 for Windows. The Mann –Whitney non-parametric U
test, univariate analysis of variances, and the two-tailed
Fisher’s exact test were used to identify the differences in
 A. Chavarrı́a et al. / Clinical Immunology 116 (2005) 271 – 278 273

the immunological response between groups. P  0.05 of 32, 25%) and single lesions were mainly located in SA
was considered significant. sulci (7 cases of 13, 53.8%) (Table 1).

Cellular and immune-inflammatory profile determined in

Results the CSF

Radiological description of NC patients General CSF description of NC patients

The radiological signs that defined each clinical group
are shown in Table 1.
Number and stage of brain cysticerci
Multiple cysticerci were found in 71.1% of the patients
(32). The remaining 28.9% had single cysticerci. While
vesicular cysticerci were found in 53.3% of the patients,
24.4% showed colloidal cysticerci and only 13.3% had
calcified cysticerci. Mixed forms were found in 8.9% of
the patients; they presented parasites in colloidal and
vesicular stages (Table 1).
Lumbar puncture showed that CSF cellularity varied
between 0 and 260 cells/ml (mean = 37.6 T 53.6) and was
greater than 5 cells/ml in 30 cases (66.7%). High CSF
inflammation was presented by 51.1% (23) of the patients.
Lymphocytes were most frequently found in CSF. Univariate
analysis of variances showed that increased CSF cellularity
was associated with SA base and intraventricular location
(P = 0.009) and to the vesicular stage of the cysticerci
(P = 0.023). Increased CSF cellularity was not associated
with parasite number. The concentration of CSF proteins
ranged between 2 and 926 mg/dl (mean = 81.2 T 167.7) and
in 21 (46.7%) patients the value was above 40 mg/dl.

Parasite location Severity is related to high CSF inflammation level and an

The exact CNS location of the cysts could not be immune-inflammatory profile
determined in 4 patients (8.9%). In these cases, it was Symptomatology was mild in 20% of the patients, mode-
impossible to distinguish between parenchymal or SA sulci rate in 60%, and severe in 20% (Table 1, Fig. 1). The rela-
location. A single parasite location was in the ventricular tionship between clinical severity and high CSF inflamation
cavities in 11.1% of the patients, in the parenchyma in 13.3%, in the NC patients is presented in Fig. 1. The percent of NC
in the SA sulci in 33.3%, and in the SA base in 20%. In cases with high inflammation level was significantly higher
contrast, six patients presented a mixed location: 3 (6.7%) in in patients with severe than in those with mild symptoms
the SA sulci and parenchyma, 2 (4.4%) in SA base and (OR = 0.036; 95% CI 0.003 –0.48, P = 0.015).
intraventricular, and 1 patient (2.2%) with intraventricular Patients with moderate symptomatology more frequently
and SA sulci cysticerci (Table 1). presented eosinophils (P = 0.07, data not shown) in the CSF
Multiple lesions were mainly located in SA base compared with mild cases. In contrast, the latter showed
cisterns (8 cases of 32, 25%) or in the SA sulci (8 cases higher levels of IL10 (P = 0.022, data not shown) and were
older (P = 0.039, data not shown). Severe patients presented
consistently higher values of protein content, cellularity, and
eosinophils than the other two groups of patients (P < 0.04,
Table 1 data not shown), and showed higher levels of IL5, IL10,
Clinical and radiological description of 45 NC patients
IgG1, IgG2, IgG3, and IgE when compared to the moderate
Severity Women/ Single/ N.P.*/Parasite N.P./Parasite cases (P < 0.05, data not shown).
Men Multiple location stage
lesions
Increased CSF cellularity is related to an
Mild 7/2 2/7 1 SA sulci 4 Vesicular
2 SA base 2 Colloidal
immune-inflammatory profile
3 Parenchyma 3 Calcified Of all measured cytokines and specific antibodies, only
1 Intraventricular those that exhibited significant differences are depicted in
1 SA sulci + parenchyma Table 2 and Figs. 2 and 3. No significant differences in
1 Parenchyma or SA sulci the concentrations of IL1h, IL4, IL12, and IFNg were
Moderate 11/16 10/17 14 SA sulci 12 Vesicular
3 SA base 8 Colloidal
detected. NC patients with increased CSF cellularity
3 Parenchyma 3 Calcified presented higher levels of protein content (P = 0.015),
1 Intraventricular 4 Mixed eosinophils (P = 0.005), and all specific IgG subclasses
1 SA base + intraventricular (P < 0.001) but not of the IgE class. Of all measured
2 SA sulci + parenchyma cytokines, only IL5 (P = 0.05), IL6 (P < 0.001), and
3 Parenchyma or SA sulci
Severe 6/3 1/8 4 SA base 8 Vesicular
IL10 (P = 0.002) were increased in NC patients with
3 Intraventricular 1 Colloidal increased CSF cellularity (Table 2).
1 SA base + intraventricular Twelve patients (26.7%) of the 45 NC patients presented
1 SA sulci + intraventricular eosinophils in the CSF as well as an increase in all four
* Number of patients. specific IgG subclasses (IgG1 P = 0.001, IgG2 P = 0.002,
274 A. Chavarrı́a et al. / Clinical Immunology 116 (2005) 271 – 278

Mixed parasite location induced a heterogeneous

immune-inflammatory response. Two patients with cyst
location in the SA base and intraventricular cavities
showed the same profile as those with cysts in the SA
base or intraventricular. They presented higher levels of
IL6, IL10, IL5, IgG2, and IgG4 (P = 0.01, P = 0.001, P =
0.07, P = 0.07, P = 0.07, respectively, data not shown)
than patients with cysticerci located only in SA sulci, and
higher levels of all IgG subclasses (P  0.046, data not
shown) and IL10 (P = 0.076, data not shown) than patients
with parenchymal NC. Mixed cyst location in the SA sulci
and parenchyma in 3 patients showed higher levels of IL4,
IL6, and IFNg (P = 0.03, P = 0.003, P = 0.002,
Fig. 1. Frequency of NC cases with high (15 cells/mm3, black bars) or respectively, data not shown) than patients with only SA
low (<15 cells/mm3, gray bars) inflammation level according to the clinical sulci cysticerci, and higher levels of IgG2, IgG3, and IL6
severity (mild, moderate, or severe). The percent of NC cases with high (P = 0.07, data not shown) than patients with only
inflammation level was significantly higher in patients with severe than
with mild symptomatology (Fischer’s exact test, P = 0.023, OR = 14).
parenchymal cysts. This mixed location did not show a
significant difference when compared to intraventricular
cysts location and presented only higher IL4 levels
IgG3 P < 0.001, IgG4 P < 0.001), IL6 (P = 0.005), CSF when compared to SA base cysts (P = 0.7, data not
proteins (P < 0.001), and cellularity (P = 0.001) (Table 2). shown).
Patients with multiple parasites exhibited increased levels
The immune-inflammatory profile in the CSF differs of IL5 and IL6 (P = 0.03, P = 0.015, respectively), while
according to gender antibody levels, though increased, were not significant as
The CSF samples analyzed were taken from 24 women
(15 –70 years old) and 21 men (16 – 68 years old). Women
had higher levels of IL5, IL6, and IL10 cytokines (P = Table 2
Immune-inflammatory profile determined in CSF of 45 NC patients
0.057, P = 0.015, P = 0.025, respectively) than men.
Although the antibody response was remarkably increased Immunological With/Without Women/ Single/ With/
profile increased Men Multiple Without
in women, the difference was not statistically significant CSF (24/21) lesions eosinophils
(IgG2 P = 0.053, IgG3 P = 0.059; Table 2). No significant cellularity (13/32) (12/33)
differences were found between men and women when the (30/15)
clinical presentation, the number, stage, and location of IgG1 (OD) 2.2/0.11a,b 1.5/0.21 0.35/1.01 2.7/0.21b
established cysticerci were compared. 2.7/0.21c 2.7/1.5 1.8/2.7 2.7/1.8
IgG2 (OD) 0.79/0.08b 0.77/0.15d 0.18/0.25 2.3/0.15b
Radiological and immune-inflammatory profile correlations 2.6/0.14 2.6/0.6 0.65/2.5 2.6/0.86
IgG3 (OD) 0.43/0.07b 0.28/0.10d 0.14/0.2 0.76/0.09b
0.76/0.09 0.79/0.4 0.36/0.6 1.3/0.45
The immune-inflammatory profile is related to parasite IgG4 (OD) 2.3/0.13b 1.8/0.31 0.31/1.4 2.7/0.2b
stage, location and disease severity 2.7/0.22 2.7/1.7 1.4/2.7 2.7/1.7
A clear immune-inflammatory profile was displayed by IL5 (pg/ml) <9.4/<9.4b <9.4/<9.4d <9.4/<9.4b <9.4/<9.4
NC patients with cysticerci located in the SA base or 36.5/<9.4 66/<9.4 <9.4/37 58.3/18
IL6 (pg/ml) 24.5/<9.4b 20/<9.4b <9.4/20.2b 38.5/<9.4b
intraventricularly. Most of them had severe symptomatology 129.5/<9.4 227/23 10.5/65 1015.3/22
and vesicular parasites, and exhibited increased levels of IL10 (pg/ml) 12.5/<9.4b 10/<9.4b <9.4/<9.4 12/<9.4
most specific IgG subclasses, IL5, IL6, and IL10 (P < 0.05) 48.3/<9.4 43/<9.4 9.8/43 208/15
(Figs. 2 and 3), and of CSF cells (P = 0.01, data not shown) CSF proteins 53/31b 37.5/39 43/35.5 68.5/33b
and eosinophils (P = 0.047, data not shown). IgG1 levels 77/43 81.8/55.5 55/66.8 131.3/45.5
CSF cells 23/6 6/15 53/6b
were higher in patients with cysticerci located in the SA base 66/41.5 69.5/59.8 123.3/37
(P = 0.05), while those having parasites with an intra- CSF 0/0b 0/0 0/0
ventricular location showed higher levels of IL10 (P = 0.065) Eosinophils 1/0 1/0 0.5/1
and IL1h (P = 0.08, data not shown). In contrast, patients Immunological features from different clinical variables were compared by
with cysticerci located in the SA sulci or parenchyma showed the non-parametric Mann – Whitney U test. Each column shows the median
lower cytokine levels, while patients with parasites and the 75% upper percentile of two groups being compared. Increased
CSF cellularity was considered when >5 cells/ml.
located in the sulci showed higher levels of IgG1, IgG2, a
Cytokine levels and antibody levels are in median values.
IgG4 (P = 0.008, P = 0.02, P = 0.02, respectively), and IFNg b
P  0.05.
(P = 0.005, data not shown) than patients with parenchymal c
The 75% upper percentile values.
d
location (Figs. 2 and 3). P  0.08. OD—optical density.
 A. Chavarrı́a et al. / Clinical Immunology 116 (2005) 271 – 278 275

Fig. 2. T. solium-specific IgG subclasses in CSF of NC cases according to parasite location (SA Base = Subarachnoid space of the base, Intraventricular, SA
Sulci = Subarachnoid space of the sulci, Parenchyma). Each patient is represented according to his/her symptomatology (mild in white, moderate in gray,
severe in black) and the respective parasite stage (vesicular in diamonds, colloidal in squares, calcified in circles, and mixed in triangles). Medians of each
location are represented by lines. The non-parametric Mann – Whitney U test was performed, only when **P  0.05 and *P  0.08 are indicated. OD, optical
density.

compared with patients with a single parasite (Table 1). Five
patients (11.1%) with radiological evidence of arachnoi-
ditis showed elevated IgG3, IgG4, IL6, CSF proteins, CSF
cells, and eosinophils (P = 0.07, P = 0.056, P = 0.068, P =
0.065, P = 0.07, P = 0.001, respectively, data not
shown).
Discussion
This study provides new insights into the immune
response related to the heterogeneous clinical and radio-
logical picture exhibited by NC patients. To better illustrate
the possible relationship between the clinical heterogeneity
of the disease and the immunological profiles, the clinical
and radiological data were included as well as a careful NC
patient classification. This is an important advance consi-
dering that previous NC studies have not reported this
medical information [15,16].
An important finding of this work is the clear relation
between increased CSF cellularity and clinical NC
severity (Fig. 1). This factor was accompanied by
increased levels of specific IgG subclasses, eosinophils,
IL5, inflammatory IL6, and the immunoregulatory cyto-
kine IL10. Most of these inflammatory NC cases occurred
when the parasite was vesicular and was established in
the SA base or in the ventricles (Figs. 2 and 3).
Interestingly, the parasite exhibited no radiological evi-
dence of damage, thus suggesting that the inflammatory
response might be ineffective. In contrast, parasites found
in the SA sulci or in the parenchyma appeared frequently
damaged with low CSF inflammation and only mild or
moderate symptomatology. The differences in parasite
condition may be the result of the interaction between the
local antigen-presenting cells (APC), immigrated lympho-
cytes and eosinophils and the cysticerci. When parasites
are located in brain parenchyma or SA sulci, a closer
contact with activated immune competent cells could
276 A. Chavarrı́a et al. / Clinical Immunology 116 (2005) 271 – 278

Fig. 3. Cytokine levels in CSF of NC cases according to parasite location (SA Base = Subarachnoid space of the base, Intraventricular, SA Sulci =
Subarachnoid space of the sulci, Parenchyma). Each patient is represented according to his/her symptomatology (mild in white, moderate in gray, severe in
black) and the respective parasite stage (vesicular in diamonds, colloidal in squares, calcified in circles, and mixed in triangles). Cytokine values are measured
in pg/ml and presented in a logarithmic scale. Medians of each location are represented by lines. The non-parametric Mann – Whitney U test was performed,
only when **P  0.05 and *P  0.08 are indicated.

favor cyst death and may explain the higher frequency of
calcified or colloidal forms in these compartments.
However, it cannot be discarded that parasite death could
be due to its own biological clock.
IL5, IL6, and IL10 are produced locally by APC of the
CNS (e.g., microglia and perivascular macrophages;
[17,18]) or by infiltrating T cells. IL5 and IL6 participate
in cell and eosinophil recruitment [19 – 21]. Patients with
parasites located in the ventricles or in the SA base or with
inflammatory CSF had higher levels of IL5 and IL6, which
could explain the increased cellularity and the presence of
eosinophils in the CSF. The recruited B cells may become
plasmatic cells and be the local source of antibodies [1],
while eosinophils could degranulate within the CNS,
damaging the parasite and the nervous tissue [22,23]. It
has been previously reported that the presence of eosino-
phils in CSF associates with severity and/or inflammatory
CSF in NC [4]. The present data support this finding and
relate the presence of eosinophils with high levels of IL6
and specific antibodies. Regarding the increased levels of
IL10, that may be also produced by regulatory CD4+ T cells
[24], and considering its immune-suppressive and regulating
functions, this cytokine could be possibly feeding back the
inflammatory effect of IL5 and IL6 in NC patients with the
immune-inflammatory profile. On the other hand, one
should not discard the possibility that, although CSF IL10
levels are high, the molecule may be not functional or
present some kind of polymorphism, as reported in patients
with multiple sclerosis, another inflammatory disease of the
CNS [25 –27].
Another point to be considered is that higher levels of
cysticercal antigens could drain to secondary lymphoid
organs more effectively when the parasite is located in
ventricles or the SA base than in the brain parenchyma.
Thus, secreted antigens could initiate an immune
response, activated T and B cells should then be able to
cross the blood –brain barrier promoting the CSF inflam-
mation [28 – 30].
Interestingly, our data also point to a sexual dimorphism
of the immune response. Although in this cohort of patients,
 A. Chavarrı́a et al. / Clinical Immunology 116 (2005) 271 – 278
there was no clinical or radiological differences between
women and men, women produced higher levels of IL5,
IL6, and IL10, revealing an increased inflammatory local
response. This observation is not due to differences in the
location or the stage of the parasite. This profile is in
agreement with previous reports in which an exacerbated
inflammatory response was found in women in CSF
cellularity and radiological imaging [13,14].
In addition, our data support the hypothesis of a
compartmentalized immune response within the CNS. In
this study, parasite location is associated with different
immune responses in the CNS. Indeed, parasites in the brain
parenchyma induced a response with low cytokines and
specific antibodies in the CSF. Parasites in the SA sulci
showed a similar profile but with higher CSF antibody
levels, while intraventricular parasites or those in the SA
base induced a pronounced response with high levels of IL5,
IL6, IL10, and specific IgG subclasses. The increased CSF
inflammation could be responsible not only for the severe
clinical symptoms induced by the parasite’s presence in
these two locations, but also for additional CNS damage as a
sequel of the disease. The balance between the benefit and
damage caused by inflammation, especially when this event
occurs in a CNS compartment, is an active area of research.
It is also relevant to consider that inflammation in the CNS
does not usually exert a repair function, rather, its tendency
is to decline to damage, which would explain most of the
CNS pathologies.
This study belongs to a program designed to identify
biological factors related to the susceptibility to NC
infection and disease. The observation of the immune-
inflammatory profile found related to NC severity allows
us to consider IL5, IL6, and IL10 as candidate genes
related to severity. Nevertheless, understanding why in
some patients, NC produces none or only mild sympto-
matology and in others, it leads to a severe clinical picture
and death, will contribute to improve the design of
therapeutic measures of NC, and perhaps to an early
treatment of the disease before the struggles between
parasite and host cause major damage to the CNS. The
CNS compartmentalized immune response opens new
perspectives to explore in the pathology of the NC and
possibly of other neurological diseases.
Acknowledgments
We thank Mercedes Baca, Marisela Hernández, and Raúl
Bobes for technical assistance, Gabriel Gutiérrez for his
valuable comments on the manuscript, Silvia Ruiz-Velasco
for the statistical advice and Roger Carrillo-Mezo for
radiological counsel. Isabel Pérez Montfort corrected the
English version of the manuscript.
This study was funded by Dirección General de Asuntos
de Personal Académico (IN220999, IN213102), Universi-
dad Nacional Autónoma de México; CONACYT (31378-
277
M), México; and Howard Hughes Medical Institute
(55000643).
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