September 1999
Volume 40, Issue 10
Free
Letters to the Editor  |   September 1999
Using Interleukin 10 to Interleukin 6 Ratio to Distinguish Primary Intraocular Lymphoma and Uveitis
Author Affiliations
  • Ronald R. Buggage
    Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland
  • Scott M. Whitcup
    Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland
  • Robert B. Nussenblatt
    Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland
  • Chi-Chao Chan
    Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland
Investigative Ophthalmology & Visual Science September 1999, Vol.40, 2462-2463. doi:https://doi.org/
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      Ronald R. Buggage, Scott M. Whitcup, Robert B. Nussenblatt, Chi-Chao Chan; Using Interleukin 10 to Interleukin 6 Ratio to Distinguish Primary Intraocular Lymphoma and Uveitis. Invest. Ophthalmol. Vis. Sci. 1999;40(10):2462-2463. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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We were interested to read the article by Ongkosuwito et al., 1 whose work expands the knowledge on cytokine expression in intraocular fluids. They used enzyme linked immunosorbent assay to examine the cytokine profile in the vitreous or aqueous humor of 44 eyes with infectious uveitis. The results were compared to 51 control samples. Increased interleukin (IL)-6 levels were found in 44 control eyes and 43 eyes with infectious uveitis. IL-10 was detected in 10 eyes with acute retinal necrosis (ARN) and 13 eyes with toxoplasmosis, but in only 3 control samples. Interferon (IFN)-γ was detected in 20 eyes with infectious uveitis and one control eye. IL-2 was found in 3 noninfectious uveitis control samples but in only one infectious uveitis case. IL-4 was undetectable in all eyes. On the basis of their results, they were unable to demonstrate a salient role for either a T-helper type 1 or a T-helper type 2 response in the pathogenesis of nonexperimental uveitis. 
In their discussion the authors reference one of our early publications 2 in which we suggested that the finding of IL-10 in the vitreous can aid in the diagnosis of primary intraocular lymphoma (PIOL) because it is absent in eyes with uveitis. They also mentioned that we reported 1 patient with ARN in whom IL-6 but not IL-10 was detected. They speculated that the absence of IL-10 in our ARN case was due to obtaining the vitreous sample late in the disease course. 
In a subsequent article 3 we reported that PIOL is strongly associated with an increased IL-10 to IL-6 ratio (greater than 1.0). Four of 13 uveitis patients had both elevated vitreal IL-6 levels and increased IL-10. In these four patients the IL-10:IL-6 ratio was less than 1.0 (0.13, 0.26, 0.67, 0.90), whereas, the vitreal IL-10:IL-6 ratio in all patients with PIOL was greater than 1.0. 
To date we have performed cytokine analysis with ELISA on 52 vitrectomy specimens from 50 patients with infectious and noninfectious uveitis. We have found elevated IL-6 levels in 31 samples (59%) but elevated IL-10 in only 6 (12%). In those 6 with increased IL-10 levels, the IL-6 was higher, with a calculated IL-10:IL-6 ratio less than 1.0 in all. Of 5 patients with ARN, only 2 had elevated IL-10 levels, whereas 4 had increased IL-6. Although IL-6 levels were increased in both toxoplasmosis cases, only one had detectable IL-10. We are unable to establish a correlation between the duration of disease at time of the vitrectomy and the IL-10 level in the patients with ARN. We calculated the vitreal IL-10:IL-6 ratio of the patients with infectious uveitis reported in Ongkosuwito’s study. All, except 2 (1.04, ARN; 1.91, inactive toxoplasmosis), had a ratio less than 1.0. 
Recently, we had a case of PIOL in which the vitreal IL-10:IL-6 ratio was less than 1.0. 4 We speculated that this represented an early stage in the tumor course. The presence of IL-10 in the eyes of uveitis patients is not diagnostic of malignancy; however, in those cases in which the vitreal IL-10 level is higher than the IL-6 the diagnosis of a PIOL should be strongly considered. 
Ongkosuwito JV, Feron EJ, van Doornik CE, et al. Analysis of immunoregulatory cytokines in ocular fluid samples from patients with uveitis. Invest Ophthalmol Vis Sci. 1998;39:2659–2665. [PubMed]
Chan CC, Whitcup SM, Solomon D, Nussenblatt RB. Interleukin-10 in the vitreous of patients with primary intraocular lymphoma. Am J Ophthalmol. 1995;120:671–673. [CrossRef] [PubMed]
Whitcup SM, Stark–Vancs V, Wittes RE, et al. Association of interleukin 10 in the vitreous and cerebrospinal fluid and primary central nervous system lymphoma. Arch Ophthalmol. 1997;115:1157–1160. [CrossRef] [PubMed]
Buggage RR, Velez G, Myers–Powell B, Shen D, Whitcup SM, Chan CC. Primary intraocular lymphoma with a low interleukin-10 to interleukin-6 ratio and heterogenous IgH gene rearrangement. Arch Ophthalmol. In press.
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