Measurement of Inflammatory Cytokines in Patients with Rheumatoid Arthritis

So-Young Kang; Myeong-Hee Kim; Woo-In Lee

doi:10.3343/kjlm.2010.30.3.301

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Kang, Kim, and Lee: Measurement of Inflammatory Cytokines in Patients with Rheumatoid Arthritis

Original Article

Korean J Leg Med 2010;30(3):301-306.

Published online: 14 January 2010

DOI: https://doi.org/10.3343/kjlm.2010.30.3.301

Measurement of Inflammatory Cytokines in Patients with Rheumatoid Arthritis

So-Young Kang, M.D., Myeong-Hee Kim, M.D., Woo-In Lee, M.D.

Department of Laboratory Medicine, The East-West Neo Medical Center, Kyung Hee University School of Medicine, Seoul, Korea

Corresponding author: Woo-In Lee, M.D. Department of Laboratory Medicine, The East-West Neo Medical Center, Kyung Hee University School of Medicine, 149 Sangil-dong, Gangdong-gu, Seoul 134-090, Korea Tel: +82-2-440-7190, Fax: +82-2-440-7195 E-mail: wileemd@hotmail.com

Revised 17 August 200930 March 2010 Accepted 23 April 2010

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background:

Inflammatory cytokines such as tumor necrosis factor alpha (TNFα) and interleukin (IL)-6 play an important role in pathophysiology of rheumatoid arthritis (RA). We investigated the possibility whether TNFα and IL-6 could be used as an objective marker reflecting treatment response in RA.

Methods:

Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and rheumatoid factor (RF) together with TNFα and IL-6 were measured in 159 specimens obtained from 95 RA patients. RA patients were divided into pre-treatment, methotrexate (MTX) and non-MTX groups by treatment regimen and into inactive and active groups by disease activity. The agreement between changes in marker levels and treatment response, and the correlation between each marker were analyzed.

Results:

IL-6 was higher in active than in inactive group of patients in all three different treatment subgroups, but TNFα was not different between the two groups. IL-6 showed a better agreement with treatment response (MTX group, K=0.58; non-MTX group, K=0.21) than ESR or CRP, whereas TNFα did not show an agreement with treatment response. IL-6 was correlated with both ESR (r=0.22) and CRP (r=0.54), but TNFα was correlated only with ESR (r=0.21).

Conclusions:

Unlike TNFα, IL-6 reflects disease activity of RA and shows a better agreement with treatment response than ESR or CRP, indicating that it has an association with clinical features of RA. Therefore IL-6 could be used as an additional marker in the evaluation of treatment response when markers like ESR or CRP show results discordant from clinical features.

Keywords: Rheumatoid arthritis, Disease activity, Tumor necrosis factor alpha, Interleukin-6

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Table 1.

Comparison of disease activity markers between non-RA, inactive RA, and active RA groups

	Non-RA group (N=53)	Inactive RA group (N=57)	Active RA group (N=102)	P value
IL-6 (pg/mL)	8.0±3.8	9.74±11.3	35.4 ±64.1∗^,†	<0.01
TNFα (pg/mL)	7.5±2.8	24.0±67.1	16.0±37.2	0.14
RF (IU/mL)	7.8±2.3	107.4±169.2∗	127.6±165.9∗	<0.01
ESR (mm/hr)	10.3±8.2	23.3±20.6∗	35.4 ±23.9∗^,†	<0.01
CRP (mg/dL)	0.13±0.27	0.39±0.81	1.94 ± 2.67∗^,†	<0.01

^∗ P<0.05 versus non-RA group;

^† P<0.05 versus inactive RA group.

Abbreviations: RA, rheumatoid arthritis; IL, interleukin; TNFα, tumor necrosis factor alpha; RF, rheumatoid factor; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.

Table 2.

Comparison of disease activity markers between inactive and active subgroup in 3 different treatment groups

	Pre-treatment group (N=15)			MTX group (N=85)			Non-MTX group (N=59)
	Inactive (N=2)	Active (N=13)	P value∗	Inactive (N=34)	Active (N=51)	P value∗	Inactive (N=21)	Active (N=38)	P value∗
IL-6 (pg/mL)	6.14±3.92	36.00±91.56	0.02	11.03±12.4	30.70±41.62	<0.01	7.58±9.00	34.00±73.66	0.04
TNFα (pg/mL)	10.52±3.11	10.84±5.04	0.8	14.65±39.52	19.23±51.10	0.27	40.92±98.34	13.59±18.01	0.94
RF (IU/mL)	139.1±90.8	164.6±206.7	0.55	60.8±78.0	119.9±154.6	0.15	171.1±245.3	126.1±165.7	0.61
ESR (mm/hr)	9.3±1.2	44.0±26.1	0.03	24.9±25.2	33.7±23.9	0.05	22.5±13.4	35.2±23.1	0.04
CRP (mg/dL)	0.02±0.01	1.95±2.79	0.01	0.30±0.39	1.59±2.08	<0.01	0.57±1.23	2.37±3.25	0.02

^∗ P value, active vs inactive groups, Mann-Whitney test.

Abbreviations: MTX, methotrexate; IL, interleukin; TNFα, tumor necrosis factor alpha; RF, rheumatoid factor; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.

Table 3.

Agreement between treatment response and each disease activity marker by K statistics in patients with serial tests performed

	Response of MTX group (N=25)	Response of non-MTX group (N=17)
IL-6	0.58	0.21
TNFα	-0.19	0.07
RF	0.30	0.10
ESR	0.28	0.10
CRP	0.25	-0.08

Kappa (K) statistics for agreement: <0.2 poor, 0.21-0.4 fair, 0.41-0.6 moderate, 0.61-0.8 good, 0.81-1.0 very good.

Abbreviations: MTX, methotrexate; IL, interleukin; TNFα, tumor necrosis factor alpha; RF, rheumatoid factor; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.

Table 4.

Agreement between disease activity markers by K statistics in patients with serial tests performed

	MTX group (N=25)				Non-MTX group (N=17)
	TNFα	RF	ESR	CRP	TNFα	RF	ESR	CRP
IL-6	-0.19	0.23	0.31	0.49	0.44	0.31	0.29	0.35
TNFα		-0.05	-0.26	-0.35		-0.08	0.10	0.25
RF			0.35	0.23			0.20	0.29
ESR				0.67				0.63

Abbreviations: MTX, methotrexate; TNFα, tumor necrosis factor alpha; RF, rheumatoid factor; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; IL, interleukin.

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