Indian Journal of Dental ResearchIndian Journal of Dental ResearchIndian Journal of Dental Research
HOME | ABOUT US | EDITORIAL BOARD | AHEAD OF PRINT | CURRENT ISSUE | ARCHIVES | INSTRUCTIONS | SUBSCRIBE | ADVERTISE | CONTACT
Indian Journal of Dental Research   Login   |  Users online: 25925

Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size         

 


 
Table of Contents   
ORIGINAL RESEARCH  
Year : 2020  |  Volume : 31  |  Issue : 6  |  Page : 840-845
Serum migration inhibitory factor levels in periodontal health and disease, its correlation with clinical parameters


1 Department of Periodontology, JSSDCH, Mysuru, Karnataka, India
2 Department of Periodontology, GDC, Bangalore, Karnataka, India

Click here for correspondence address and email

Date of Submission07-Dec-2018
Date of Decision08-Jan-2020
Date of Acceptance02-Jul-2020
Date of Web Publication22-Mar-2021
 

   Abstract 


Objectives: Periodontal infections are an important risk factor for systemic disease and are driven primarily by the cytokines. Migration Inhibitory Factor (MIF) is a key cytokine which mediates acute and chronic inflammation alongside, a molecular link between chronic inflammation and immune mediated conditions. Hence, the present study was carried to measure the serum MIF levels in periodontal health, disease and to correlate the levels with the clinical parameters. Material and Methods: Sixty subjects were divided into three groups (each group n = 20) based on the gingival index (GI), probing pocket depth (PPD), and clinical attachment level (CAL) as group I healthy; group II gingivitis; and group III chronic periodontitis. The serum MIF level was measured using quantitative sandwich enzyme immunoassay technique. Results: Highest level was detected in Group III with a mean of 71.8 ng/ml and the lowest in group I (6.1 ng/ml). Serum MIF levels did not correlate with the clinical parameters. Conclusion: Increased serum MIF levels in chronic periodontitis patients suggest its role as an inflammatory biomarker and may have a role in inflating the systemic inflammation. Summary: Serum Migration inhibitory factor can be used as an inflammatory marker for periodontal disease

Keywords: Cytokine(s), periodontal-systemic disease interactions, periodontitis

How to cite this article:
Ganganna A, Subappa A, Bhandari P. Serum migration inhibitory factor levels in periodontal health and disease, its correlation with clinical parameters. Indian J Dent Res 2020;31:840-5

How to cite this URL:
Ganganna A, Subappa A, Bhandari P. Serum migration inhibitory factor levels in periodontal health and disease, its correlation with clinical parameters. Indian J Dent Res [serial online] 2020 [cited 2021 Apr 19];31:840-5. Available from: https://www.ijdr.in/text.asp?2020/31/6/840/311668



   Introduction Top


Periodontitis is a multifactorial disease caused by host–microbial interactions leading to the destruction of supporting tissues around teeth. The interplay between the host, microbes, and virulence factors is extremely complex wherein immune response not only restricts the invading parasite but participates in destruction of host cells with robust release of cytokines.

Cytokines are soluble proteins produced by immune cells having both autocrine, paracrine effects, and in some instances endocrine effect. Macrophage migration inhibitory factor (MIF) is one such cytokine involved in macrophage and T-cell activation, cell growth, apoptosis, tumor angiogenesis and carbohydrate metabolism.[1],[2],[3] It is produced by macrophages, T-cells, endothelial cells of several organs, and pituitary gland upon inflammatory and stress stimulation.[4] MIF acts on receptor CD74 and controls the recruitment of inflammatory cells via CXCR2 and CXCR4 signalling.[5],[6] Furthermore, it exerts pro-inflammatory effects through its tautomerase and oxidoreductase activity.[7],[8] Its action is also linked to Jun activation domain binding protein-1 (JAB1) and tumor suppressor protein p 53.[9]

MIF is released into circulation after a brief exposure to cytokines, oxidized lipids, lipopolysaccharide (LPS), and is believed to control the inflammatory “set point” by regulating the release of proinflammatory cytokines like tumor necrosis factor–α (TNF-α), Interleukin -1β, Interleukin-8, Cyclooxygenase -2 (COX-2), Nitric oxide, and products of arachidonic acid pathway.[10] It has actions similar to TNF-α, they induce each other; work together and also amplify the inflammatory response. Additionally, amount of LPS required to release MIF is 10-100 times lower than those needed to induce TNF-α, explaining its increased sensitivity toward bacterial challenge.[11] However, uncontrolled secretion of large amount of cytokines during sepsis or infection is referred to as “Cytokine storm” and among these cytokines MIF is as a key player.[12]

MIF was the first cytokine to be identified (1966)[13] Since then, numerous studies have suggested its role in myocardial infarction, tumor angiogenesis, obesity, Type II diabetes, rheumatoid arthritis, etc.[14],[15],[16],[17]>/sup> Madeira et al. stated that MIF contributes significantly to the progression of periodontal bone loss by directly affecting differentiation of osteoclasts and thereby enhancing osteoclastic activity.[18] Involvement of MIF in the expression of matrix metalloproteinase-2 (MMP) in human gingival fibroblasts during periodontitis was assessed and was concluded that MMP-2 is not triggered by MIF.[19] Another study evaluated the levels of the innate immunity-related markers with MIF in serum and saliva from patients with generalized Aggressive periodontitis (AgP), gingivitis, and healthy individuals, but failed to show any significant difference in MIF levels among the groups.[20] Furthermore, studies have highlighted the production of MIF which is modified by age in response to periodontopathic bacteria[21] but till date, no study has reported serum MIF levels in health, gingivitis and chronic periodontitis.

Accumulated evidence indicates that patients with periodontitis present with increased systemic inflammation with raised serum inflammatory markers when compared with controls and has been implicated in modulating many systemic conditions.[22] In view of these findings, it is rational to study the levels of these markers in the peripheral circulation of subjects with periodontal disease. Therefore, our study was designed to know the serum MIF levels in periodontal health, disease and to correlate MIF with the clinical parameters.


   Material and Methods Top


Sixty subjects (n = 60; 20 participants in each group; age range: 18–40 years) from the Department of Periodontology, JSS Dental College and Hospital, Mysuru were enrolled for the study during September 2015 to March 2016. The participants in periodontitis (Group III) and gingivitis group (Group II) were selected from the outpatient section who were referred for diagnosis and treatment. Healthy group (Group I) was derived from staff, house surgeons, and graduate students of college. Patients with diabetes, cardiovascular diseases, smoking habits, tumors, or any other systemic disease were excluded. The following exclusion criteria was also used: (1) pregnancy and menopause; (2) use of medication like antibiotics, anti-inflammatory drugs; (3) periodontal therapy in the preceding three months; (4) acute conditions like abscess and pericoronitis; and (5) AgP. The periodontal status of the participants was assessed according to the classification of the American Academy of Periodontology.[23] Approval of the ethics committee was obtained from the institutional review board (Jagadguru Sri Shivrathreshwara Dental College and Hospital, Mysuru) and written informed consent was obtained from those who agreed to participate voluntarily. Research was conducted in full accordance with the world medical association declaration of Helsinki.

First examiner (AS) recorded an extensive medical history to exclude/include individuals with complete documentation of extra and intra-oral findings. Clinical examiner (AG) performed all the clinical measurements where-in each subject underwent full-mouth periodontal probing and charting. Intraoral peri-apical radiographs were taken to assess the bone loss (dichotomously: presence or absence) to differentiate patients with chronic periodontitis from other groups. Subjects were categorized into three groups based on the gingival index (GI) (Loe and Silness, 1963), probing pocket depth (PPD), clinical attachment level (CAL), and radiographic evidence of bone loss.[24]

Group I: Subjects with clinically healthy periodontium (GI = 0, PPD ≤3 mm and CAL = 0).

Group II: Subjects with gingival inflammation (GI >1, PPD ≤3 mm and CAL = 0)

Group III: Subjects who showed clinical signs of gingival inflammation GI >1, PPD ≥5 mm and radiographic bone loss with CAL ≥1 mm

PPD and CAL were measured using a William's graduated periodontal probe.

Sample collection and storage

Five millilitres of venous blood was collected from each patient by veni-puncture in the antecubital fossa. Samples were collected into blood collection tubes containing no anticoagulant and were allowed to clot for 30 min at room temperature and centrifuged at 1,000 × g for 15 min. The serum was extracted and stored in plastic vials at ≤ -70°C.

Estimation of serum MIF

The MIF level in serum was measured using quantitative sandwich enzyme immunoassay technique (R&D Systems Human MIF Quantikine Elisa Kit). The serum samples and standards (recombinant human MIF) were incubated (2h at room temperature) in wells pre-coated with primary anti-human MIF antibody. After incubation, the wells were washed three times, and horseradish peroxidase–conjugated polyclonal antibodies against MIF were added with 2h incubation at room temperature. Finally substrate solution (stabilized hydrogen peroxide and tetramethylbenzidine) was added which is a colour reagent. After 30 min, 50 μL of stop solution was added to each well and the optical density was determined of each well using a microplate reader set at 450 nm. All samples, controls, and standards were assayed in duplicate to avoid any error.

Statistical analysis

Data analysis was carried out using statistical package for social science (SPSS 22). Test for validity of normality assumption using ShapiroWilk test was carried out and the test was valid. One-way analysis of variance was used to test the difference between three independent groups and further pair–wise comparison between the groups was tested using Tukey test. Pearson's correlation coefficient was calculated to know the relationship between MIF and the clinical parameters. P value < 0.05 was considered as statistically significant. Sample size was calculated for hypothesis testing between two means using nMaster software (Dept of Biostatistics, Christian Medical College, Vellore). It was computed to be 16 with an assumed mean difference of 3.2 between the groups at 5% alpha error and 80% power for an effect size of 1.03. However, the sample size was rounded- off to 20, anticipating 20% non-response.


   Results Top


The descriptive statistics of the study groups are presented in [Table 1]. All the samples tested positive for the presence of MIF with the highest mean in Group III, that is, 71.8 ng/ml, Group II showed an intermediate level (48.6 ng/ml) and the lowest was in group I (6.1 ng/ml). Serum MIF concentrations was found to be higher, approximately eight folds in gingivitis group (group II) and by ten folds in chronic periodontitis group as compared to healthy group (group I). Tukey test for pair wise comparison of serum MIF showed that the differences were statistically significant between groups I and II, groups I and III and groups II and III (P < 0.005) as shown in [Table 2].
Table 1: Descriptive statistics of the study population showing mean and standard deviation for the age, GI, PPD, CAL and serum MIF levels

Click here to view
Table 2: Pair wise comparison using Tukey test for serum MIF

Click here to view


Pearson's correlation coefficient test was carried out to find correlation between clinical parameters and serum MIF levels but no significant correlation was found between the two as shown in [Table 3].
Table 3: Pearson correlation coefficient test comparing serum MIF with GI, PPD and CAL

Click here to view


Confidence interval was calculated for differentiating the limits of serum MIF values in different groups. Differentiating values with probability 0.95 for different groups were: Healthy-less than or equal to 6.1 ng/ml, Gingivitis- more than 6.1 ng/ml and less than 71.8 ng/ml, chronic periodontitis-equal to or more than 71.8 ng/ml.


   Discussion Top


With an array of interactions and functions, MIF has engendered researchers for decades since 1966. In course of time, complexities associated with its abundant source and simultaneous cloning of other immune-mediators [e.g., Interleukin-4(IL-4), TNF-α] truncated the general interest in MIF. Initial studies unveiled the pro-inflammatory functions of MIF and highlighted its role in potentiating endotoxemia when coinjected with LPS.[25] Surprisingly, subsequent studies displayed an ambiguity in its secretion from the same pituitary cell that release ACTH, a hormone which stimulates the release of glucocorticoids– a potent anti-inflammatory mediator. This apparent confusion was resolved by experiments stating that glucocorticoids in low concentration directly induce MIF release and at high concentrations, its secretion is shut off.[26] Hence; the enormous research around MIF instated this study in estimating its levels in health, gingivitis, and periodontitis with simultaneous correlation with clinical parameters.

Periodontitis presents a local microbial burden initiating both local and systemic inflammation. It involves direct tissue damage and also affects indirectly through bacterial induction of host inflammatory- immune response. Studies by Loos et al.,[27] D' Aiuto et al.,[28] have stated that patients with periodontitis present increased systemic inflammation, as indicated by raised serum levels of inflammatory cytokines when compared with controls. The possible morbidity and mortality from systemic diseases may be reduced by improving periodontal health therefore, it is important to explore the level of these markers in peripheral circulation of subjects with periodontal disease.

Elevated plasma MIF levels are associated with atherosclerotic lesions- as it acts as a potent angiogenic factor by upregulating the adhesion molecules {soluble vascular cell adhesion molecule (sVCAM-1) and soluble intercellular adhesion molecule (sICAM-1)},[29] carcinogenesis –by mimicking the action of oncogene RAS protein,[30] diabetes-”by programming insulin resistance,[31] Multiple Organ dysfunction syndrome (MODS)-”by triggering an exaggerated inflammatory response and many more conditions,[32] Multiple inflammatory sources contribute to circulating MIF where periodontitis also plays its part. It tends to be a “silent” disease and the occult infection can have the same effect as a more clinically evident infection perturbs, hence strategies aimed at reducing these sources should be encouraged.

Nonnenmacher et al.[21] in an experimental gingivitis study showed increase in GCF MIF concentration and a positive correlation with the oral plaque index. Our data has shown that gingivitis patients had increased serum MIF levels compared to healthy subjects and periodontitis group having higher levels than the gingivitis group. This proportional increase from health to disease can be attributed to the maximum spill-over of MIF into systemic circulation from the local tissue in periodontitis group in-comparison with gingivitis and healthy group, which can also be correlated with the severity of the disease. The variability of MIF level among the patients of each group could be related to the different stages of disease- activity during serum collection. The presence of MIF in the healthy group could be attributed to the basal circulating levels as they are expressed by the immune cells like monocytes/macropahges, T-cells, B-cells and by also secreted by pituitary gland in response to stress stimuli.[25]

In the present study the influence of age and gender on the MIF concentration was minimized by including the equal number of males and female with an age of 18–40 years in each group. Further, this study included three groups (healthy, gingivitis, and chronic periodontitis), to better understand the pattern of variation in different stages of periodontal disease.

Gurkan A et al.[33] determined GCF levels of MIF with other cytokines in metabolic syndrome patients (MetS) with gingivitis and stated that GCF MIF levels did not differ between MetS patients with gingivitis compared to gingivitis patients without MetS. However, gingivitis patients had increased GCF MIF levels compared to healthy subjects and was in accordance with the study of Nonnenmacher et al. Madeira et al. suggested the role of MIF in controlling the replication of Aggregatebacter actinomycetemcomitans (Aa) alongside, enhancing the bone resorptive activity by stimulating osteoclasts.[18] However, the present study is the first to report increased serum MIF levels in patients with periodontal disease.

Significant correlations indicating a direct relationship between serum MIF level and clinical parameters was not proven in our study which should be interpreted carefully, further longitudinal studies can validate the present findings. The differentiating values with probability 0.95 have shown that serum MIF levels ≤6.1 ng/ml suggests periodontal health, from 6.1 ng/ml to 71.8 ng/ml gingivitis and levels ≥71.8 ng/ml suggests chronic periodontitis. Thus, its role as an inflammatory biomarker in periodontal disease can be proposed.

In medical literature, the interplay between MIF and other inflammatory cytokines have been documented extensively however, its role in periodontal diseases have to be investigated with related interventions to unveil the distinctive cascade. The possible association of developing other systemic conditions due to increased circulating MIF can pave the way to further studies in serum and other local tissues to explore the actual potential-risk associated with it. Corollary to this, strategies blocking MIF may be useful in suppressing the “cytokine storm” and thereby controlling the inflammation.


   Conclusion Top


In summary, accumulated evidence suggest the role of MIF in inflammatory and immune mediated system with varied expression and function. Although investigations of MIF in periodontal disease are less, the available data emphasizes its participation in initiation and progression of disease hence, therapies directed towards MIF pathways may open newer avenues in treating periodontal pathologies. In the present study, we demonstrated elevated serum MIF level in periodontitis group compared to gingivitis and healthy group, which might trigger low-grade systemic inflammation. Growing evidence linking periodontal health and systemic inflammation warrants further research to understand this biologic mechanism.

Future Perspective

D-dopachrome tautomerase (D-DT also called as MIF-2) has been identified as a second MIF super-family member having similar actions as MIF and binds to the same trans-membrane receptor CD 74. In this context, it is worthwhile to carry clinical research of the two proteins simultaneously to attain better understanding.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Acknowledgement

Authors would like to acknowledge the support received by JSS academy of higher education and research in conducting this research. We would also like to thank Dr. Nandlal.B for his encouragement and guidance.

Financial support and sponsorship

The work was supported by JSS Academy of Higher Education and Research, Mysuru.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Calandra T, Roger T. Macrophage migration inhibitory factor: A regulator of innate immunity. Nat Rev Immunol 2003;3:791-800.  Back to cited text no. 1
    
2.
Chesney JA, Mitchell RA. 25 Years on: A retrospective on migration inhibitory factor in tumor angiogenesis. Mol Med 2015;21 Suppl: S19-24.  Back to cited text no. 2
    
3.
Benigni F, Atsumi T, Calandra T, Metz C, Echtenacher B, Peng T, et al. The proinflammatory mediator macrophage migration inhibitory factor induces glucose catabolism in muscle. J Clin Invest 2000;106:1291-300.  Back to cited text no. 3
    
4.
Wistow GJ, Shaughnessy MP, Lee DC, Hodin J, Zelenka PS. A macrophage migration inhibitory factor is expressed in the differentiating cells of the eye lens. Proc Natl Acad Sci U S A 1993;90:1272-5.  Back to cited text no. 4
    
5.
Bernhagen J, Krohn R, Lue H, Gregory JL, Zernecke A, Koenen RR, et al. MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment. Nat Med 2007;13:587-96.  Back to cited text no. 5
    
6.
Bucala R, Shachar I. The integral role of CD74 in antigen presentation, MIF signal transduction, and B cell survival and homeostasis. Mini Rev Med Chem 2014;14:1132-8.  Back to cited text no. 6
    
7.
Rosengren E, Aman P, Thelin S, Hansson C, Ahlfors S, Björk P, et al. The macrophage migration inhibitory factor MIF is a phenylpyruvate tautomerase. FEBS Lett 1997;417:85-8.  Back to cited text no. 7
    
8.
Kleemann R, Kapurniotu A, Frank RW, Gessner A, Mischke R, Flieger O, et al. Disulfide analysis reveals a role for macrophage migration inhibitory factor (MIF) as thiol-protein oxidoreductase. J Mol Biol 1998;280:85-102.  Back to cited text no. 8
    
9.
Fingerle-Rowson G, Koch P, Bikoff R, Lin X, Metz CN, Dhabhar FS, et al. Regulation of macrophage migration inhibitory factor expression by glucocorticoids in vivo. Am J Pathol 2003;162:47-56.  Back to cited text no. 9
    
10.
Mitchell RA, Liao H, Chesney J, Fingerle-Rowson G, Baugh J, David J, et al. Macrophage migration inhibitory factor (MIF) sustains macrophage proinflammatory function by inhibiting p53: Regulatory role in the innate immune response. Proc Natl Acad Sci U S A. 2002;99:345-50.  Back to cited text no. 10
    
11.
Bucala R. MIF rediscovered: Cytokine, pituitary hormone, and glucocorticoid-induced regulator of the immune response. FASEB J 1996;10:1607-13.  Back to cited text no. 11
    
12.
Pang T, Cardosa MJ, Guzman MG. Of cascades and perfect storms: The immunopathogenesis of dengue haemorrhagic fever-dengue shock syndrome (DHF/DSS). Immunol Cell Biol 2007;85:43-5.  Back to cited text no. 12
    
13.
David JR. Delayed hypersensitivity in vitro: Its mediation by cell-free substances formed by lymphoid cell-antigen interaction. Proc Natl Acad Sci U S A 1966;56:72-7.  Back to cited text no. 13
    
14.
White DA, Fang L, Chan W, Morand EF, Kiriazis H, Duffy SJ, et al. Pro-inflammatory action of MIF in acute myocardial infarction via activation of peripheral blood mononuclear cells. PLoS One 2013;8:e76206.  Back to cited text no. 14
    
15.
Tomiyasu M, Yoshino I, Suemitsu R, Okamoto T, Sugimachi K. Quantification of macrophage migration inhibitory factor mRNA expression in non-small cell lung cancer tissues and its clinical significance. Clin Cancer Res 2002;8:3755-60.  Back to cited text no. 15
    
16.
Morrison MC, Kleemann R. Role of macrophage migration inhibitory factor in obesity, insulin resistance, Type 2 diabetes, and associated hepatic co-morbidities: A comprehensive review of human and rodent studies. Front Immunol 2015;6:308.  Back to cited text no. 16
    
17.
Onodera S, Tanji H, Suzuki K, Kaneda K, Mizue Y, Sagawa A, et al. High expression of macrophage migration inhibitory factor in the synovial tissues of rheumatoid joints. Cytokine 1999;11:163-7.  Back to cited text no. 17
    
18.
Madeira MFM, Queiroz-Junior CM, Costa GM, Santos PC, Silveira EM, Garlet GP, et al. MIF induces osteoclast differentiation and contributes to progression of periodontal disease in mice. Microbes Infect 2012;14:198-206.  Back to cited text no. 18
    
19.
Hirschfeld J, Howait M, Movila A, Parėina M, Bekeredjian-Ding I, Deschner J, et al. Assessment of the involvement of the macrophage migration inhibitory factor-glucocorticoid regulatory dyad in the expression of matrix metalloproteinase-2 during periodontitis. Eur J Oral Sci 2017;125:345-54.  Back to cited text no. 19
    
20.
Lira-Junior R, íztürk Ví, Emingil G, Bostanci N, Boström EA. Salivary and serum markers related to innate immunity in generalized aggressive periodontitis. J Periodontol 2017;88:1339-47.  Back to cited text no. 20
    
21.
Nonnenmacher C, Helms K, Bacher M, Nüsing RM, Susin C, Mutters R, et al. Effect of age on gingival crevicular fluid concentrations of MIF and PGE2. J Dent Res 2009;88:639-43.  Back to cited text no. 21
    
22.
Ebersole JL, Machen RL, Steffen MJ, Willmann DE. Systemic acute-phase reactants, C-reactive protein and haptoglobin, in adult periodontitis. Clin Exp Immunol 1997;107:347-52.  Back to cited text no. 22
    
23.
Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol 1999;4:1-6.  Back to cited text no. 23
    
24.
Aruna G. Estimation of N-terminal telopeptides of type I collagen in periodontal health, disease and after nonsurgical periodontal therapy in gingival crevicular fluid: A clinico-biochemical study. Indian J Dent Res 2015;26:152-7.  Back to cited text no. 24
[PUBMED]  [Full text]  
25.
Bernhagen J, Calandra T, Mitchell RA, Martin SB, Tracey KJ, Voelter W, et al. MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. Nature 1993;365:756-9.  Back to cited text no. 25
    
26.
Calandra T, Bernhagen J, Metz CN, Spiegel LA, Bacher M, Donnelly T, et al. MIF as a glucocorticoid-induced modulator of cytokine production. Nature 1995;377:68-71.  Back to cited text no. 26
    
27.
Loos BG, Craandijk J, Hoek FJ, Wertheim-van Dillen PM, van der Velden U. Elevation of systemic markers related to cardiovascular diseases in the peripheral blood of periodontitis patients. J Periodontol 2000;71:1528-34.  Back to cited text no. 27
    
28.
D'Aiuto F, Ready D, Tonetti MS. Periodontal disease and C-reactive protein-associated cardiovascular risk. J Periodontal Res 2004;39:236-41.  Back to cited text no. 28
    
29.
Amin MA, Haas CS, Zhu K, Mansfield PJ, Kim MJ, Lackowski NP, et al. Migration inhibitory factor up-regulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 via Src, PI3 kinase, and NFkappaB. Blood 2006;107:2252-61.  Back to cited text no. 29
    
30.
Mitchell RA, Metz CN, Peng T, Bucala R. Sustained mitogen-activated protein kinase (MAPK) and cytoplasmic phospholipase A2 activation by macrophage migration inhibitory factor (MIF). Regulatory role in cell proliferation and glucocorticoid action. J Biol Chem 1999;274:18100-6.  Back to cited text no. 30
    
31.
Kim B-S, Pallua N, Bernhagen J, Bucala R. The macrophage migration inhibitory factor protein superfamily in obesity and wound repair. Exp Mol Med 2015;47:e161.  Back to cited text no. 31
    
32.
de Mendonça-Filho HTF, Pereira KC, Fontes M, de Souza Aranha Vieira DA, de Mendonça MLAF, de Almeida Campos LA, et al. Circulating inflammatory mediators and organ dysfunction after cardiovascular surgery with cardiopulmonary bypass: A prospective observational study. Crit Care 2006;10:R46.  Back to cited text no. 32
    
33.
Gürkan A, Eren G, Çetinkalp Ş, Akçay YD, Emingil G, Atilla G. Monocyte chemotactic protein-1, RANTES and macrophage migration inhibitory factor levels in gingival crevicular fluid of metabolic syndrome patients with gingivitis. Arch Oral Biol 2016;69:82-8.  Back to cited text no. 33
    

Top
Correspondence Address:
Dr. Aruna Ganganna
#1004, Sri Durga Parameshwari Krupa, Mysuru, Karnataka - 570 029
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdr.IJDR_896_18

Rights and Permissions



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
 
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  
 


    Abstract
   Introduction
   Material and Methods
   Results
   Discussion
   Conclusion
    References
    Article Tables

 Article Access Statistics
    Viewed268    
    Printed10    
    Emailed0    
    PDF Downloaded23    
    Comments [Add]    

Recommend this journal