0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation | Journal Club

Effects of Azithromycin on Gene Expression Profiles of Proinflammatory and Anti-inflammatory Mediators in the Eyelid Margin and Conjunctiva of Patients With Meibomian Gland Disease

Lili Zhang, MD, PhD1; Zhitao Su, MD, PhD1; Zongduan Zhang, MD, PhD1; Jing Lin, MD, PhD1; De-Quan Li, MD, PhD1; Stephen C. Pflugfelder, MD1
[+] Author Affiliations
1Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas
JAMA Ophthalmol. 2015;133(10):1117-1123. doi:10.1001/jamaophthalmol.2015.2326.
Text Size: A A A
Published online

Importance  Topical application of azithromycin suppresses expression of proinflammatory mediators while restoring transforming growth factor β1 (TGF-β1) levels as evaluated by eyelid margin and conjunctival impression cytology.

Objective  To explore the effects of azithromycin therapy on expression of proinflammatory and anti-inflammatory mediators in meibomian gland disease (MGD).

Design, Setting, and Participants  Case-control study performed in a clinic setting from August 17, 2010, to December 31, 2010. Sixteen patients with posterior blepharitis and conjunctival inflammation due to MGD were treated with azithromycin, 1%, drops for 4 weeks. Impression cytology of the lower eyelid margin and tarsal conjunctiva to measure cytokine expression by quantitative real-time polymerase chain reaction as well as tear collection to measure matrix metalloproteinase 9 (MMP-9) activity were performed once in 8 asymptomatic healthy control participants and 5 times in the 16 symptomatic patients (every 2 weeks for 8 weeks), before, during, and after azithromycin treatment.

Exposure  Azithromycin, 1%, drops for 4 weeks.

Main Outcomes and Measures  Cytokine expression in the eyelid margin and conjunctiva, and MMP-9 activity in tears.

Results  Compared with a 1-time measurement of 8 healthy participants, among 16 symptomatic patients, the mean (SD; 95% CI) fold change of expression of proinflammatory mediators interleukin 1β (IL-1β), IL-8, and MMP-9 increased to 13.26 (4.33; 11.14-15.38; P < .001), 9.38 (3.37; 7.73-11.03; P < .001), and 13.49 (4.92; 11.08-15.90; P < .001), respectively, in conjunctival cells and to 11.75 (3.96; 9.81-13.69; P < .001), 9.31 (3.28; 7.70-10.92; P < .001), and 11.52 (3.50; 9.81-13.24; P < .001), respectively, in the eyelid margin of patients with MGD. In contrast, the mean (SD; 96% CI) fold change of expression of TGF-β1 messenger RNA (mRNA) decreased to 0.58 (0.25; 0.46-0.70; P = .02) and 0.63 (0.14; 0.56-0.70; P = .02) in conjunctival and eyelid margin cells, respectively, of patients with MGD. Azithromycin, 1%, caused a change in the expression pattern of these mediators toward normal levels during 4 weeks of treatment. Levels of IL-1β, IL-8, and MMP-9 mRNA remained suppressed, although they rebounded toward pretreatment values 4 weeks after azithromycin withdrawal. Expression of TGF-β1 increased during treatment and remained at levels similar to the healthy controls after drug withdrawal. Change in tear MMP-9 activity was similar to the pattern of MMP-9 transcripts.

Conclusions and Relevance  While the study did not control for potential confounding factors over time independent of the intervention that may have contributed to the results, topical azithromycin suppressed expression of proinflammatory mediators and increased expression of TGF-β1 to normal levels. Increased TGF-β1 expression may contribute to the anti-inflammatory activity of azithromycin in MGD.

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Figures

Place holder to copy figure label and caption
Figure 1.
Cytokine Expression Profiles in Meibomian Gland Disease (MGD) by Quantitative Real-Time Polymerase Chain Reaction

Increased expression of proinflammatory mediators interleukin 1β (IL-1β), IL-8, and matrix metalloproteinase 9 (MMP-9) and decreased transforming growth factor β1 (TGF-β1) messenger RNA (mRNA) by conjunctival (A) and eyelid margin (B) cells in patients with MGD compared with healthy controls. Horizontal lines indicate mean; error bars, standard deviation.

aP < .001 vs healthy controls.

bP < .05 vs healthy controls.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Effects of Azithromycin on Cytokine Profiles in Meibomian Gland Disease (MGD)

Messenger RNA (mRNA) levels of proinflammatory mediators interleukin 1β (IL-1β), IL-8, and matrix metalloproteinase 9 (MMP-9) and transforming growth factor β1 (TGF-β1) in conjunctival (A) and eyelid margin (B) cells, measured once in healthy controls and 5 times (every 2 weeks before, during, and after azithromycin treatment) in patients with MGD. Data points indicate mean; error bars, standard deviation.

aP < .001 vs healthy controls.

bP < .001 vs pretreatment levels.

cP < .01 vs pretreatment levels.

dP < .05 vs healthy controls.

eP < .05 vs pretreatment levels.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.
Tear Matrix Metalloproteinase 9 (MMP-9) Activity

Azithromycin suppressed MMP-9 activity in tear samples from patients with meibomian gland disease (MGD) at 5 times (every 2 weeks before, during, and after azithromycin treatment). A healthy control group without MGD was included for comparison. Horizontal lines indicate mean; error bars, standard deviation.

aP < .001 vs healthy controls.

bP < .001 vs pretreatment levels.

Graphic Jump Location

Tables

References

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

621 Views
0 Citations
×

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
Jobs
brightcove.createExperiences();