Cytokine production by T cells infiltrating in the eye of uveitis patients.
The capacity of T cells to produce cytokines was investigated using T-cell clones (TCCs) established from infiltrating cells in the aqueous humor (AH) or peripheral blood mononuclear cells (PBMC) of patients with Vogt-Koyanagi-Harada (VKH) disease or sarcoidosis. The cytokines produced and tested in the study were interleukin (IL)-1alpha, IL-6, IL-8, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and granulocyte monocyte colony stimulating factor (GM-CSF). All TCCs (n = 9) from AH of VKH patients spontaneously produced significantly larger amounts of IL-6, IL-8, and IFN-gamma than TCCs from healthy donor PBMC. All TCCs (n = 9) from AH of the sarcoidosis patient spontaneously produced significantly larger amounts of IL-1alpha, IL-6, and IL-8 than TCCs from healthy donor PBMC. In addition, the effects of antiinflammatory drugs on the cytokine production by the TCCs were investigated. Hydrocortisone significantly suppressed the production of IL-6, IL-8, and GM-CSF by TCCs from AH of VKH patients. Tacrolimus also significantly suppressed the production of IL-8 and GM-CSF by the TCCs. FTY720, an experimental drug, suppressed only GM-CSF production by TCCs from AH of VKH patients. Diclofenac failed to suppress the production of any cytokines by any TCCs. All tested drugs did not suppress the production of cytokines by TCCs from the sarcoidosis patient. These results thus suggest that cytokines produced by T cells infiltrating in the eye may play an important role in the pathogenesis of uveitis.
Sakaguchi
M
M
Department of Ophthalmology, Kurume University School of Medicine, Fukuoka, Japan.
Sugita
S
S
Sagawa
K
K
Itoh
K
K
Mochizuki
M
M
D000328:Adult; D000368:Aged; D001082:Aqueous Humor / Q000166:cytology; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000068876:Fingolimod Hydrochloride; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D011409:Propylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D013110:Sphingosine / Q000031:analogs & derivatives; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use; D014605:Uveitis / Q000188:drug therapy / Q000276:immunology*
D016207:Cytokines; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D009883:Ophthalmic Solutions; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; D006854:Hydrocortisone; D016559:Tacrolimus