IL-8 may be systemic anti-inflammatory marker

November 1, 2008

An analysis of data from a study of eye disease in Latinos provides additional evidence that interleukin-8 (IL-8) may play a role in the development or progression of age-related macular degeneration.

Key Points

Los Angeles-Interleukin-8 (IL-8) may be a systemic anti-inflammatory marker in Latinos with high-risk non-exudative age-related macular degeneration (AMD). Data from the Los Angeles Latino Eye Study (LALES), a population-based prevalence study of eye disease in Latinos (primarily Mexican-Americans) aged 40 or more years, showed a significant increase in IL-8 among participants with bilateral soft drusen, whereas no association existed between levels of C-reactive protein (CRP) and AMD in a multivariate analysis, according to Michael Javaheri, MD, PhD. He is a clinical instructor at the Doheny Eye Institute and Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles.

Although the prevalence of AMD in Latinos increases with age, Dr. Javaheri said, it does so to a lesser degree than in Caucasians. This fact was learned through earlier LALES studies in which changes in early AMD; retinal pigment epithelium abnormalities; large drusen; and soft, distinct, and indistinct drusen were analyzed. Studies also have shown that the prevalence of early and advanced AMD were significantly associated with increasing age, although Latinos were found to have an extremely low prevalence of advanced AMD.

Inflammatory markers

"In the last 10 years, our knowledge of inflammation in AMD has grown exponentially, with increasing studies showing that AMD does share a significant amount of risk factors with cardiovascular disease," he said.

These risk factors include nutritional lipids, body mass index, and smoking, which has been linked to a two-times greater risk of AMD. New studies also have shown that inflammatory markers such as CRP, complement factor H, IL-6, and IL-8 are involved in the development of late AMD.

For their analysis, the LALES investigators analyzed the levels of CRP and IL-8 in the blood of a subset of patients with unilateral or bilateral soft, indistinct drusen or early AMD, indicating that they are at high risk of progression to advanced AMD. Patients were excluded if their disease was characterized by hard, distinct drusen or drusen with pigment abnormalities.

The study population included 118 eligible cases and 118 matched controls. All patients had fundus photographs that were graded for AMD characteristics using a modified Wisconsin Age-Related Maculopathy Grading System. Patients provided blood samples that were evaluated for IL-8 and CRP. Controls were matched on age, body mass index, sex, presence of hypertension, presence of cardiovascular disease, and smoking status. Patients with neovascular AMD were excluded due to the relatively small sample size.

Logistic regression was performed to determine the independent relationship between IL-8, CRP, and AMD; the analysis was adjusted for history of chronic illness related to systemic inflammation, including arthritis, asthma, stroke, and myocardial infarction.

Statistically significant results

Results of the univariate analysis showed that the differences between cases and controls were statistically significant for IL-8 (p < 0.001) and CRP (p < 0.001). Mean IL-8 values were 1572.6 pg/ml for cases and 1065.6 pg/ml for controls. The mean CRP values were 2289.2 ng/ml for cases and 2089.8 ng/ml for controls.

In multivariate analysis using conditional logistic regression and controlling for the chronic diseases, IL-8 remained significantly associated with bilateral soft indistinct drusen AMD (p = 0.04), whereas CRP did not. For every 1,000 pg/ml increase in IL-8, the odds ratio of getting early AMD increased by 15%, Dr. Javaheri said.

"We were able to show that IL-8 was significantly associated with early AMD, while CRP was not. Future studies are needed to elucidate the exact role of IL-8 in early AMD and in progression," he concluded.

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