| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland
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)-
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 publications2 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 article3 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.
References
1 1Department of Ophthalmology, Academic Medical Centre Amsterdam, The Netherlands 2 2Department of Ophthalmo-Immunology, Netherlands Ophthalmic Research Institute, Amsterdam 3 3Rotterdam Eye Hospital 4 4F. C. Donders Institute for Ophthalmology, University Hospital Utrecht 5 5Department Ophthalmology, University Hospital Nijmegen 6 6Department Ophthalmology, University Hospital Maastricht
We appreciate the calculations reported by Drs. Buggage,
Nussenblatt, Chan, and Whitcup based on the data of our recent
article,1
in which we described the detection of
interleukin (IL)-2, IL-4, IL-6, IL-10, and interferon (IFN)- in
patients with acute retinal necrosis (ARN) and toxoplasmosis
and in control subjects. In their letter Buggage et al. speculate that
the fact that the IL-10:IL-6 ratio was greater than 1.0 in two of our
patients could possibly indicate an early stage in the tumor course. We
believe that this assumption is unlikely; since the samples were taken
in 1995, we have been able to evaluate the follow-up of both patients.
In one patient, who had acute retinal necrosis, the sample was taken
only 2 weeks after the start of symptoms. This sample also was examined
pathologically and revealed normal lymphocytes, monocytes, plasma
cells, and a few erythrocytes. Further evaluation revealed that after 2
years, the bulbus was enucleated because of phtisis bulbi, and
pathologic examination did not reveal signs of an intraocular lymphoma.
Furthermore, the sample we used for the detection of cytokines also
revealed a positive polymerase chain reaction for varicella-zoster
virus, and intraocular production of IgG antibodies against this virus
also could be established, confirming the diagnosis of ARN caused by
varicella-zoster virus.
The other patient with an IL-10:IL-6 ratio exceeding 1.0 had ocular toxoplasmosis, and further follow-up did not show any signs of an intraocular lymphoma. After our manuscript was submitted, we extended our cytokine studies and also have had the opportunity to test two samples from patients with a suspected intraocular lymphoma (in collaboration with Professor Marc de Smet). The IL-10:IL-6 ratio was 329 and 6, and pathologic examination of the ocular fluid samples confirmed the diagnosis of intraocular lymphoma in both cases. Routine tests for infectious causes of uveitis were negative. Thus, we agree that an IL-10:IL-6 ratio may become an important test in the diagnosis of intraocular lymphoma but would like to point out that the exact cutoff ratio indicating a positive test result still has to be established and may vary between laboratories. Furthermore, we would like to stress that tests excluding infectious causes should be performed at the same time.
References
This article has been cited by other articles:
|
|
 |
|
  Z. Li, S. P. Mahesh, D. F. Shen, B. Liu, W. O. Siu, F. S. Hwang, Q.-C. Wang, C.-C. Chan, I. Pastan, and R. B. Nussenblatt Eradication of Tumor Colonization and Invasion by a B Cell-Specific Immunotoxin in a Murine Model for Human Primary Intraocular Lymphoma Cancer Res., November 1, 2006; 66(21): 10586 - 10593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Curnow, F. Falciani, O. M. Durrani, C. M. G. Cheung, E. J. Ross, K. Wloka, S. Rauz, G. R. Wallace, M. Salmon, and P. I. Murray Multiplex Bead Immunoassay Analysis of Aqueous Humor Reveals Distinct Cytokine Profiles In Uveitis Invest. Ophthalmol. Vis. Sci., November 1, 2005; 46(11): 4251 - 4259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R R Buggage, D F Shen, C-C Chan, and D G Callanan Propionibacterium acnes endophthalmitis diagnosed by microdissection and PCR Br. J. Ophthalmol., September 1, 2003; 87(9): 1190 - 1191. [Full Text] [PDF]
|
|
|
|
 |
|
 E. K. Akpek, C. S. Foster, R. R. Buggage, S. M. Whitcup, R. B. Nussenblatt, and C.-C. Chan Primary Intraocular Lymphoma With a Low Interleukin 10 to Interleukin 6 Ratio and Heterogeneous IgH Gene Arrangement Arch Ophthalmol, May 1, 2000; 118(5): 731 - 732. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
