CLINICAL & BASIC RESEARCH

SQU Med J, December 2010, Vol. 10, Iss. 3, pp. 361-369, Epub. 14th Nov 10 
Submitted 27th Feb 10
Revision ReQ. 7th July 10, Revision recd. 15th July 10
Accepted 19th Sept 10

1Al-Salaam Hospital, Mosul City, Iraq; 2Department of Pharmacology, Mosul College of Medicine, University of Mosul, Mosul City, Iraq 
*Corresponding Author email: imadpharma@yahoo.com

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عماد عبد اجلبار ذنون، ضياء احمد طه
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 150 75
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


aBstract: Objectives: The objective of this study was to evaluate the influence of acute pulmonary tuberculosis 
and the effect of drug therapy on markers of oxidative stress (malondialdehyde [MDA] and total antioxidant status 
[TAS]), C-reactive protein (CRP) and iron body status indices. Methods: Forty patients with active pulmonary 
tuberculosis from the Advisory Clinic for Chest and Respiratory Diseases in Mosul City, Iraq,were included in 
this study, with fifty healthy age and sex matched subjects as controls. Assessment of serum concentrations of 
MDA, TAS, CRP, serum iron, total iron binding capacity, transferring saturation percent and ferritin were done for 
both patients and controls. After two months of therapy with a daily dose of isoniazid 75 mg, rifampicin 150mg, 
pyraziamide 400 mg, and ethambutol 275 mg, the same parameters were reassessed for the patients. Results: After 
two months of therapy, there was a significant reduction in the levels of MDA, CRP, and ferritin, with a significant 
increase in the TAS, serum iron, and transferring saturation percentage with an insignificant effect on the total iron 
binding capacity in comparison with the patients’ pre-therapy values. Conclusion: Active pulmonary tuberculosis is 
associated with oxidative stress; the increase in the levels of CRP indicated that pulmonary tuberculosis is associated 
with an inflammatory response. The initial two months therapy led to significant improvement in oxidative stress 
and suppression of inflammatory responses. Newly diagnosed cases of pulmonary tuberculosis often had chronic 
anaemia of inflammation, but this therapy resulted in a significant correction of such anaemia.

Keywords: Pulmonary tuberculosis; Oxidant/antioxidant status; C-reactive protein; Iron status

Antioxidant Status, C-Reactive Protein and Iron 
Status in Patients with Pulmonary Tuberculosis

Dhia A Taha1 and *Imad A-J Thanoon2

CLINICAL & BASIC RESEARCH

Advances in Knowledge
1. Newly diagnosed cases of pulmonary tuberculosis are associated with oxidative stress as indicated by enhanced lipid peroxidation 

(reflected in the malondialehyde level) and reduced total antioxidant status.
2. They are also associated with an intense inflammatory response as indicated by increase levels of acute phase protein C-reactive protein.



Antioxidant Status, C-Reactive Protein and Iron Status in Patients with Pulmonary Tuberculosis

362 | SQU Medical Journal, December 2010, Volume 10, Issue 3

Mycobacteria are capable of  inducing reactive oxygen species production by activating both 
mononuclear and polymorphonuclear phagocytes 
that may possess antimicrobial activity.  
The enhanced level of free radical production, 
although designed to combat the invader, has the 
potential to damage the host; however, host tissue 
damage is limited by the concurrent enhancement of 
the antioxidant defences of the host.1 In tuberculosis 
(TB) patients, there are also some reports of poor 
antioxidants defence that may expose to oxidative 
host tissue damage.2,3 

C-reactive protein (CRP), an acute phase 
protein, is synthesised by hepatocytes in response 
to proinflammatory cytokines in particular IL-6.4 
CRP has been reported to be significantly elevated 
in patients with active tuberculosis (TB), normalising 
over time on therapy, thereby correlating with 
clinical response.5,6 The  physiological roles of CRP 
are numerous, one of the critical functions being 
its importance in host defense. In the presence of 
calcium, CRP specifically binds to polysaccharides 
such as phosphocholine moieties present on the cell 
surface of many pathogenic microbes.7 CRP binding 
activates the classical complement pathway and 
initiates opsonization, phagocytosis, and lyses of 
invading cells. CRP can also augment cell mediated 
cytotoxicity i.e. amplify the immune response.7

Iron has a crucial role in TB infection. On the 
one hand, it influences both the innate and acquired 
immune response, and it is required for bacterial 
replication.8 Indeed, iron levels can be a determining 
factor during infection because overload in human 
and mice results in exacerbation of the disease.9 The 
concentration in serum of iron and the iron-binding 
protein, transferrin, varies markedly in different 
pathological and physiological conditions. Both 
concentrations (with transferrin being expressed 
as total iron-binding capacity) with or without 
serum ferritin are used in identifying various types 
of anaemia.10 Both iron deficiency and anaemia 
of chronic inflammation may coexist in patients 

with pulmonary tuberculosis. Chronic anaemia 
of inflammation has several features in common 
with iron deficiency anaemia, thus confusing 
the aetiological diagnosis. Low serum iron and 
transferrin saturation percentages, characteristic 
laboratory findings of iron-deficiency anaemia, are 
also seen in chronic inflammatory anaemia.11 It is, 
therefore, difficult to establish the exact mechanism 
of associated anaemia in pulmonary tuberculosis 
patients by the routine investigations for diagnosis of 
anaemia.

The aims of this study were to assess the influence 
of an initial two months of treatment on serum levels 
of lipid peroxidation products: malondialdehyde 
(MDA), total antioxidant status (TAS), CRP, and 
indices of iron body status (serum iron, total iron 
binding capacity (TIBC), transferrin saturation 
percentage, and serum ferritin) in patients with active 
pulmonary TB in comparison to controls.

Methods
Patients included in this study, which was undertaken 
from December 2007 to April 2008, were obtained 
from Advisory Clinic for Chest and Respiratory 
Diseases in Mosul City, Iraq. The analytical work 
was performed in the Department of Pharmacology, 
College of Medicine, at the University of Mosul. 
Approval was obtained from Ethical Committees of 
the main Health Centre in Ninevah, Mosul-City, and 
the College of Medicine of the University of Mosul, 
Iraq.

Eligibility for entry into the study included typical 
symptoms of pulmonary TB: fibrocavitary lung 
infiltrate on chest radiograph and at least one sputum 
specimen staining positive with Ziehl-Neelsen for 
acid-fast bacilli. All patients included in the study 
were non-smokers and had no history of drug usage 
(including vitamins, iron, or antibiotics) at the time of 
initial assessment. They also had no history of blood 
transfusion in the previous 6 months and no recent 
history of blood loss. Additional criteria for females 
included neither being pregnant nor lactating, nor 

3. Newly diagnosed cases of pulmonary tuberculosis often had chronic anaemia of inflammation, although the possibility of iron deficiency 
anaemia cannot be ruled out.

Application to Patient Care
1. Initial therapy with antituberculosis drugs is very important to suppress oxidative stress, acute inflammation and chronic anaemia of 

inflammation in patients with active pulmonary tuberculosis.



Dhia A Taha and Imad A-J Thanoon

Clinical and Basic Research | 363

menstruating at the time of blood collection. Patients 
with a history of previous treatment for tuberculosis 
were not included in order to exclude those with 
previous lung fibrosis or infection with multidrug-
resistant tuberculosis. Also, patients were excluded 
who had co-existing lung pathology, defined as a 
history of previous respiratory disease or clinical or 
radiological evidence of lung pathology other than 
tuberculosis, cardiac disease or metabolic problems 
including chronic liver disease, renal failure or 
diabetes mellitus. Out of 48 patients interviewed 
and examined, only forty patients with active TB 
(29 males, 11 females, age range from 19-70 years), 
with a mean age of  39.95 ± 13.46 years consented to 
participate in this study. They were followed up for 
two months after receiving the initial course of anti-
tuberculosis drugs described below. 

Fifty apparently healthy volunteers (36 males 
and 14 females, age range from 18–70 years), with a 
mean age of 43.88 ± 14.26 years, and with no previous 
history of tuberculosis, were recruited as controls to 
establish the normal values for MDA, TAS, CRP, 
serum iron, total iron binding capacity, transferrin 
saturation percentage, and serum ferritin.

After diagnosis, patients with pulmonary 
tuberculosis were treated according to the standard 
protocol at the Advisory Clinic. Patients were given 

4 tablets of Rimstar®, a fixed-dose tablet containing 
4 anti-tuberculosis drugs (isoniazid (INH) 75 mg, 
rifampicin 150 mg, pyraziamide 400 mg, ethambutol 
275 mg) to be swallowed daily before breakfast for the 
initial two months. Approximately 10 ml of venous 
blood was drawn using disposable plastic syringes 
from tuberculosis patients prior to initiation of anti-
tuberculosis treatment, and again at the end of the two 
month intensive phase of treatment, and transferred 
immediately into disposable plain tubes. The serum 
was separated after centrifugation of the blood and 
kept frozen at –20 oC to be analysed. Blood samples 
from the healthy control subjects were collected and 
processed in the same way. 

Serum MDA levels were estimated using a 
thiobarbituric acid (TBA) assay,12 and TAS according 
to the method described by Miller et al.,13 using a 
Randox TAS kit (Randox Laboratories Ltd., Antrim, 
UK). CRP was determined semi-quantitatively by 
slide agglutination using a CRP Latex kit (Chemelex, 
Spain). Serum iron was measured colorimetrically 
(Direct method)14 using a Ferene assay kit (Biolabo 
Reagents, France). TIBC was measured using a 
REF 92308 assay kit (Biolabo Reagents, France). 
Transferrin saturation percentage was calculated 
according to the following formula15:

Transferrin  
saturation % 

=
Serum Iron concentration x 100

TIBC

Finally, serum ferritin was measured, using the 
ELFA technique (enzyme linked fluorescent assay), 
with VIDAS instrument, and a Ferritin kit (both from 
Bio Merieux, France).

The data of the study, subjected to statistical 
analysis, were expressed as mean ± standard deviation 
(SD). Statistical comparisons were performed using 
the Student’s t-test. The Fisher-Freeman-Halton 
test was used to compare the results of CRP of 
tuberculosis patients with the controls. The paired 
Wilcoxon Z-test was used to compare the results of 
CRP in tuberculosis patients before and after therapy. 
Linear regression analysis and Pearson correlation 
coefficients(r), were performed to determine the 
relationships between different parameters. Analysis 
of variance was performed for determining the 
relationships between CRP and other parameters. 
A P-value of <0.05 was considered to be statistically 
significant.

Table 1: Concentrations of malondialdehyde, total 
antioxidant status and iron body status indices 
in healthy controls and patients with pulmonary 
tuberculosis before and after therapy

Parameters Control  
(n = 50)

TB cases (n = 40)

Before 
therapy

After 
therapy

MDA 
(µmol/l)

1.24 ± 0.17 3.18 ± 
0.58***

2.82 ± 
0.60***   §§§

TAS 
(mmol/l)

1.86 ± 0.30 1.06 ± 
0.12***

1.27 ± 
0.11***  §§§

Iron (µg/dl) 99.12 ± 27.5 55.73 ± 
16.78***

76.95 ± 2
8.29***  §§§

TIBC (µg/dl) 397.1 ± 68.5 394.8 ± 
148.7

376.7 ± 
136.0

Transferrin 
saturation %

25.58 ± 8.4 15.89 ± 
7.0***

21.37 ± 8.7* 
§§§

Ferritin (ng/
ml)

183.1 ± 65.6 441.76 ± 
319.4***

185.64 ± 
129.1 §§§

Note: Results are expressed as mean ± SD
Legend: MDA = malondialdehyde; *** Significant difference from 
control at P <0.001; TAS = total antioxidant status; §§§ Significant 
difference from before at P <0.001; TIBC = serum iron, total iron 
binding capacity; * = Significant difference from control at P <0.05.



Antioxidant Status, C-Reactive Protein and Iron Status in Patients with Pulmonary Tuberculosis

364 | SQU Medical Journal, December 2010, Volume 10, Issue 3

Results
The serum levels of MDA, TAS, iron, total iron 
binding capacity, transferrin saturation percent, 
ferritin and CRP from healthy subjects and patients 
with pulmonary TB before and after two months of 
therapy are shown in Tables 1 and 2. 

The serum levels of MDA were significantly 
higher (P <0.001) and TAS were significantly lower (P 
<0.001) in patients with pulmonary TB before starting 
therapy in comparison with the control group. After 
two months of therapy, there was a highly significant 
reduction (P <0.001) in the serum MDA with a highly 
significant increase (P <0.001) in the serum TAS from 
initial pre-treatment levels. 

Both serum iron and transferrin saturation 
percentages were significantly lower (P <0.001), 
and serum ferritin concentration was significantly 
higher (P <0.001) in patients with pulmonary 
TB before starting therapy in comparison with 
the control subjects. However, TIBC showed 
insignificant differences compared to the control 
values. After two months therapy, there was highly 
significant elevation in the levels of serum iron 
(P <0.001) and transferrin saturation percentage 
(P <0.001) and a highly significant reduction in 
ferritin levels (P <0.001); however, TIBC showed 
insignificant differences after therapy.

As shown in Table 2, the serum levels of CRP 
were significantly higher (P <0.001) in patients with 
pulmonary TB before starting therapy in comparison 
with the control group and, after two months therapy, 
there was a highly significant reduction (P <0.001) in 

CRP levels.
Regarding correlations between different 

biochemical parameters, Figures 1, 2 and 3 show 
the relationships between MDA, TAS and serum 
ferritin in patients with pulmonary TB (before 
and after therapy) and in the control group.  
There was a highly significant negative correlation  
(r = -0.852; P <0.001) between serum MDA and 
TAS, a highly significant positive correlation  
(r = 0.348; P <0.001) between serum ferritin and 
MDA and a highly significant negative correlation  
(r = -0.345; P <0.001) between serum ferritin and 
TAS in patients with pulmonary TB (before and after 
therapy) and in the control group.

Tables 3, 4 and 5 show the relationships between 
CRP, MDA, TAS and serum ferritin in patients 
with pulmonary TB (before and after therapy) and 

Table 2: Comparison of C-reactive protein (CRP) 
concentrations between healthy controls and patients 
with pulmonary tuberculosis before and after therapy

CRP
mg/l

Control  
(n = 50)

Before drug 
(n = 40)

After drug  
(n = 40)

   No.     %    No.      %    No.       %

<6 39 78.0 0 0.0 12 30.0

6 9 18.0 6 15.0 19 47.5

12 2 4.0 11 27.5 7 17.5

24 0 0.0 10 25.0 2 5.0

48 0 0.0 4 10.0 0 0.0

96 0 0.0 9 22.5 0 0.0

P-value versus control <0.001 <0.001

 

y = -0.3499x + 2.2448

r = -0.852

p<0.001

0

0.5

1

1.5

2

2.5

3

0 1 2 3 4 5

MDA (µmol/l)

TA
S 

(m
m

ol
/l)

Before drug

After drug

Control

 
Figure 1: Relationship between MDA and TAS in the studied cases and control. 
Legend: MDA = malondialdehyde; TAS = total antioxidant status



Dhia A Taha and Imad A-J Thanoon

Clinical and Basic Research | 365

in the control group. There was a highly significant 
correlation between CRP and MDA, between CRP 
and TAS and between CRP and serum ferritin 
in patients with pulmonary TB (before and after 
therapy) and in the control group.

Discussion
In the present study, it was observed that the serum 
MDA levels were significantly high and the antioxidant 
status was significantly low in newly diagnosed 
patients with pulmonary TB as compared to healthy 
controls. It was also observed that the administration 
of antimicrobial agents to such patients for a period of 
2 months was associated with a significant reduction 
in MDA concentrations and a significant increase 
in total antioxidant status. Although considerable 
improvement was noted in these parameters, still 

there were significant differences from the control 
values. Our finding of enhanced lipid peroxidation 
product and reduced TAS provides evidence for 
the presence of oxidative stress in newly diagnosed 
patients with active pulmonary tuberculosis. 
Furthermore, the decrease in levels of MDA, with 
a concomitant increase in TAS after two month 
of therapy seen in our study, may indicate a good 
response to therapy. 

Plit et al. found that even after 6 months of 
successful chemotherapy, pulmonary TB is still 
associated with increased levels of circulating lipid 
peroxides and low plasma concentrations of vitamin 
E.3 These findings are in line with our results of 
significant differences in MDA concentrations and 
TAS between patients after two months of therapy 
and the control group which indicate that oxidative 
stress were ongoing even after two months of 

 

y = 0.0015x + 1.9244
r = 0.348
p<0.001

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

0 200 400 600 800 1000 1200 1400

Ferritin (ng/ml)

M
D

A 
(µ

m
ol

/l)
Be fore  drug
Afte r drug
Control

 
Figure 2: Relationship between ferritin and MDA in the studied cases and control.
Legend: MDA = malondialdehyde

 
y = -0.0006x + 1.594

r = - 0.345

p<0.001

0

0.5

1

1.5

2

2.5

3

0 200 400 600 800 1000 1200 1400

Ferritin (ng/ml)

TA
S 

(m
m

ol
/l)

Before drug

After drug

Control

 
Figure 3: Relationship between ferritin and total antioxidant status in the studied cases and control

Legend: TAS = total antioxidant status



Antioxidant Status, C-Reactive Protein and Iron Status in Patients with Pulmonary Tuberculosis

366 | SQU Medical Journal, December 2010, Volume 10, Issue 3

chemotherapy.
In an attempt to kill Mycobacteria, host cells 

(namely macrophages, neutrophils and monocytes)
generate huge amounts of reactive oxygen species 
(ROS).16 One of the manifestations of these reactive 
species is lipid peroxidation. These high levels 
of reactive species are often cytotoxic and may 
cause host tissue damage such as lung fibrosis and  
lung dysfunction in patients with pulmonary TB 
if antioxidant defences of the host are deficient.17 

Malnutrition is more common in patients with 
pulmonary TB than in the healthy subjects, and 
could possibly explain the low levels of antioxidant 
potential. Furthermore, patients with tuberculosis are 
unable to produce a sufficient amount of antioxidant 
to cope with their increased oxidative stress.18

 In the present study, TAS was measured instead 
of determining individual antioxidant enzymes and 
molecules. Low levels of TAS were observed in 
pulmonary TB. This might be due to malnutrition 
or exhaustion in an attempt to neutralise the heavy 
load of free radical in these patients. This study 
showed a highly significant negative correlation  
between serum MDA levels and TAS in patients 
with pulmonary TB (before and after therapy) 
and in the control group. This suggests increased 
utilisation by reactive oxygen species as an important 
contributing factor to the lower concentrations of 
antioxidants in tuberculosis patients.18,19 In fact, the 
combination of malnutrition (leading to decreased 
“supplementation” of antioxidants) and enhanced 
ROS generation (leading to increased utilisation of 
these compounds) may represent a pathogenic loop 
that results in markedly enhanced oxidative stress 
during tuberculosis infection.18,19   

This study also showed that the CRP 
concentrations in newly diagnosed patients were 

significantly higher than those of healthy controls 
and that the administration of anti-tuberculosis drug 
therapy for an initial two months was associated 
with a significant reduction in serum levels. CRP has 
been reported to be significantly elevated in patients 
with active TB, normalising over weeks on therapy, 
thereby correlating with clinical response.5,6 Higher 
CRP concentrations have also been associated with 
more severe tuberculosis TB and poor prognosis.20 
This observation is supported by reports that patients 
with more severe lung dysfunction, as evidenced by 
lung cavitation, had significantly higher CRP levels 
than patients without cavitation.21 Mycobacterium 
tuberculosis and its components have been shown to 
stimulate mononuclear phagocytes in vitro to release 
IL-6, which are regarded as inflammatory mediators. 
IL-6 is known to induce hepatic acute phase reactants 
(including CRP). Several clinical and laboratory 
findings support the significant relation between IL-6 
and CRP.22 Bekker et al. suggested that the decrease in 
CRP concentration in patients treated for pulmonary 
tuberculosis is paralleled by a similar reduction in 
plasma cytokines such as IL-6, the principal cytokine 
that induces CRP synthesis, and that the fall in serum 
CRP concentration during treatment of pulmonary 
tuberculosis might be correlated with the resolution 
of the systemic inflammatory process.23   

In the present study, the serum iron levels and 
transferrin saturation percentage were observed to be 
significantly lower in patients with active pulmonary 
tuberculosis before starting therapy in comparison 
with the controls. This study also demonstrated that 
after therapy the serum levels of both parameters 
showed significant elevation. Although considerable 
improvements were reported in these parameters, still 
there were highly significant differences in serum iron 
levels and mildly significant differences in transferrin 

Table 3: Relationship between C-reactive protein (CRP) 
and malondialdehyde (MDA) in the studied cases and 
control group

CRP n          MDA,  
        Mean ±SD

P value

<6 51 1.56 ±0.70

<0.001

6 34 2.51 ±0.88

12 20 2.72 ±0.78

24 12 3.30 ±0.46

48 4 3.00 ±0.12

96 9 3.44 ±0.65

Table 4: Relationship between C-reactive protein (CRP) 
and total antioxidant status (TAS) in the studied cases 
and control.

CRP n         TAS,  
        Mean ±SD

P value

<6 51 1.74 ±0.37

<0.001

6 34 1.36 ±0.33

12 20 1.25 ±0.27

24 12 1.10 ±0.10

48 4 1.00 ±0.08

96 9 1.01 ±0.11



Dhia A Taha and Imad A-J Thanoon

Clinical and Basic Research | 367

saturation percentages after two months of therapy 
in comparison to control values. Kassu et al. found 
that the concentrations of iron were significantly 
lower in the serum of patients with pulmonary 
TB in comparison with the control group, with no 
significant differences at the end of the intensive 
phase of chemotherapy.24 Although these are in 
agreement with our findings of lower pre-treatment 
serum iron levels in patients in comparison to the 
healthy controls, they disagree with our finding of a 
significant increase in serum iron levels after therapy.  

The hypoferraemia in TB patients may be induced 
by the shift of iron from a transferrin-bound available 
state to a ferritin-incorporated storage state.24 The 
condition may have evolved as a cytokine-mediated 
defence against microbial pathogens, effectively 
withholding iron from microbes, which incidentally 
also deprives erythroid precursors of their iron supply.25 
Gobin and Horwitz suggested that Mycobacteria 
acquire their iron from the host’s own transferrin/
ferritin iron binding proteins, and they achieve this by 
releasing a type of iron-capturing siderophore called 
an exochelin. This, in turn, transfers and donates the 
iron back to the mycobactins which exist in the cell 
walls of the Mycobacteria.26 Baynes et al. suggested 
that patients with pulmonary tuberculosis are often 
anaemic due to restriction of available iron by the 
host.5 This restriction occurs as a major component of 
the host natural immunity and is characterised by the 
induction of an acute phase response that limits the 
amount of circulating iron, primarily accomplished 
by iron sequestration. The sequestration of iron by 
the host also limits iron-induced cellular damage to 
the host itself through binding by serum proteins 
such as transferrin, ferritin and lactoferrin. Overall, 
an attempt is made by the host to induce an iron 
deficiency upon the pathogen.27 The low serum iron 
levels seen in this study may also be attributed to low 

levels of dietary iron intake, low socioeconomic status 
and blood loss by haemoptysis. 

Values of TIBC are usually high in iron deficiency 
anaemia and low in inflammatory anaemia.28 The 
TIBC reflects transferrin, the protein to which 
virtually all iron in the blood is bound.29 In this study, 
we assessed TIBC as an indirect measurement of 
serum transferrin concentrations, and found no 
significant differences in TIBC between patients with 
pulmonary TB before and at the end of intensive 
phase of therapy and control subjects. Al-Omar and 
Oluboyede reported low initial (pre-treatment) TIBC 
levels in patients with pulmonary tuberculosis.30 
Also, Devi et al. reported low TIBC concentrations 
in patients with pulmonary tuberculosis, and they 
attributed their findings to an acute phase response 
since transferrin is a negative acute phase protein 
and serum levels may be decreased in inflammatory 
conditions.11 

Our results also showed a significantly higher 
serum ferritin concentration in tuberculosis patients 
before starting therapy in comparison with healthy 
controls. There was also a significant reduction in 
the serum levels at the end of the intensive phase 
of chemotherapy. Ferritin concentration in blood 
is considered to be a specific indicator of body 
iron stores;31 however, the concentration can rise 
following an inflammatory response, irrespective 
of iron status. Some reports indicated that ferritin 
synthesis is stimulated in pulmonary tuberculosis as a 
consequence of the inflammatory process.32 Al-Omar 
and Oluboyede attributed the rise in serum ferritin 
levels in their study to two factors: first, increased 
production by monocytes and macrophages, 
monocytosis having been observed in pulmonary 
TB; second, serum ferritin is an acute phase protein 
that increases in inflammatory conditions.30 In favour 
of this conclusion, we found a positive correlation 
between serum ferritin and CRP. The raised ferritin 
levels seen in our patients point more towards the 
possibility of anaemia of inflammation, although an 
association with iron deficiency anaemia cannot be 
completely ruled out. In patients with anaemia of 
chronic inflammation, there appear to be a defect in the 
freeing of iron from macrophages, the loading of iron 
onto plasma transferrin, or both. Reticuloendothelial 
iron is plentiful in bone marrow macrophages, but 
this iron is not available to erythroid precursors.33

This study showed that after two months of 
therapy there were significant corrections in serum 

Table 5: Relationship between C-reactive protein (CRP) 
and ferritin in the studied cases and control group

CRP N            Ferritin, 
         Mean ±SD

P value

<6 51 142.18 ±88.00

<0.001

6 34 94.37 ±97.43

12 20 203.24 ±189.68

24 12 419.09 ±425.85

48 4 561.07 ±323.15

96 9 653.39 ±281.07



Antioxidant Status, C-Reactive Protein and Iron Status in Patients with Pulmonary Tuberculosis

368 | SQU Medical Journal, December 2010, Volume 10, Issue 3

iron levels, transferrin saturation percent and serum 
ferritin despite the fact that our patients received no 
iron supplementation. These observations give rise 
to the possibility that the anaemia in our patients is 
of chronic inflammation rather than iron deficiency 
anaemia; however, the possibility of iron deficiency 
anaemia cannot be ruled out, since the only effective 
treatment for anaemia of chronic inflammation is 
correction of the underlying disorder. 

Both CRP and ferritin have been reported to 
reflect the extent of oxidative stress and inflammation 
in individual patients and may be useful markers 
of disease activity and mortality risk.34 In the 
present study, we have investigated the relationship 
between markers of oxidative stress and markers of 
inflammation in TB patients and in healthy controls. 
Subjects with higher serum ferritin and CRP 
concentrations, indicative of greater inflammatory 
response in such individuals, also had higher serum 
MDA levels and lower TAS than those with lower 
serum ferritin and CRP concentrations. This picture 
was observed in the figures which showed that 
both serum CRP and ferritin levels were positively 
correlated with lipid peroxidation product and 
negatively correlated with TAS.

Nguyen-Khoa et al. conducted a study to 
investigate the role of inflammation in exacerbating 
oxidative stress in haemodialysis patients, and they 
found that plasma CRP levels were correlated positively 
with plasma levels of lipid peroxidation products, and 
negatively with plasma α-tocopherol and albumin 
levels.35 They suggested that inflammatory processes 
induce an increase production of ROS which lead 
to the consumption of fat-soluble antioxidants and 
subsequently to the generation of lipid peroxidation 
products. They also found that the increase in plasma 
ferritin levels observed in haemodialysis patients was 
not associated with an increase in the level of lipid and 
protein oxidative stress markers. Ferritin expression 
is modulated by a variety of conditions associated 
with oxidative stress that act either directly on gene 
expression or indirectly via the modification of iron 
responsive elements activity. Superoxide anions 
produced during oxidative stress can mobilise iron 
from ferritin and this may augment the intensity of 
oxidative stress by catalysing the production of highly 
toxic hydroxyl radicals by Fenton and Haber-Weiss 
reactions.36

Conclusion 
This study concluded that pulmonary tuberculosis 
is associated with oxidative stress as indicated 
by enhanced lipid peroxidation products (MDA) 
and reduced total antioxidant status and that the 
administration of anti-tuberculosis treatments for 
the initial two months (intensive phase) reduces 
the serum MDA level, elevates TAS and decreases 
oxidative stress. The increased levels of acute phase 
proteins (CRP and serum ferritin) indicate that 
pulmonary TB is associated with an inflammatory 
response and that the administration of treatment for 
the initial two months brings about suppression of 
the inflammatory response with significant reduction 
in these proteins. This study also concluded that 
newly diagnosed patients with pulmonary TB often 
had anaemia of chronic inflammation as shown by 
disturbances in iron body status indices, although 
the possibility of iron deficiency anaemia cannot be 
ruled out, and that therapy resulted in a significant 
correction of such anaemia.

conflict of interest
The authors reported no conflict of interest.

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