Vascular cell adhesion molecule-1-mediated matrix metalloproteinase-2 induction in peripheral blood T cells is up-regulated in patients with HTLV-I-associated myelopathy.

We investigated whether matrix metalloproteinase-2 (MMP-2) is induced in peripheral blood T cells after their contact with tumor necrosis factor-alpha (TNF-alpha)-stimulated glioblastoma cell line (T98G), expressing vascular cell adhesion molecule-1 (VCAM-1), in patients with HTLV-I-associated myelopathy (HAM) compared to control patients with other neurological disorders (OND). Gelatin zymography revealed that the incremental ratio of gelatinolytic activity of MMP-2 in culture supernatants derived from T cells cocultured with TNF-alpha-stimulated T98G to that of supernatants derived from cultures of T cells alone was significantly higher in HAM patients than in control patients with OND. Immunoblot analysis of immunoprecipitates of culture supernatant showed that increased gelatinolytic activity of MMP-2 was due to increased production of MMP-2 protein in T cells. Increased gelatinolytic activity of MMP-2 in T cells of HAM patients was blocked by pretreatment of TNF-alpha-stimulated T98G with anti-VCAM-1 antibody before coculture with T cells, indicating that MMP-2 induction was VCAM-1-mediated. Although no significant differences were noted in the percentage of VLA-4-positive cells in cultured T cells between HAM patients and control patients with OND, our results indicate that VCAM-1-mediated MMP-2 induction is up-regulated in T cells of HAM patients.

Elevated levels of interleukin-12 and interferon-gamma in patients with human T lymphotropic virus type I-associated myelopathy.

The levels of interleukin-12 (IL-12) (p70 heterodimer), total IL-12 (p70 heterodimer plus p40 chains), interferon-gamma (IFN-gamma) as Th1 cytokine, and those of interleukin-4 (IL-4) and interleukin-10 (IL-10) as Th2 cytokines in sera and cerebrospinal fluid (CSF) from 22 patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) were compared with those of 22 patients with other neurological diseases (OND), including nine anti-HTLV-I-seropositive carriers. Both serum IL-12 (total and p70 heterodimer) and CSF IFN-gamma, measured by the enzyme-linked immunosorbent assay (ELISA), were significantly elevated in patients with HAM as compared to the patients with OND, including the anti-HTLV-I-seropositive carriers. Serum IFN-gamma also was significantly elevated in the HAM patients as compared to the controls. There was no significant difference in the CSF levels of IL-12 (total and p70 heterodimer) between the HAM patients and controls, whereas, for the Th2 cytokines IL-4 was detected in the CSF of four anti-HTLV-I-seropositive carriers of the 13 control patients but not in any of the patients with HAM. No significant difference was found in the serum levels of IL-4 and IL-10, nor in the CSF levels of IL-10 in the patients with HAM and in the controls. These findings indicate that in patients with HAM, the immunological balance of helper T lymphocytes between Th1 and Th2 is toward Th1 in the periphery and that Th1-mediated immunological status in the central nervous system is involved in the pathogenesis of HAM.

Downward extension of the lacrimal gland under the bulbar conjunctiva after trabeculectomy.

PURPOSE: To describe two cases in which the lacrimal gland was considered to extend downward under the bulbar conjuctiva following trabeculectomy. PATIENTS AND METHODS: We report two patients who complained of epiphora after trabeculectomy. A biopsy was performed on the tissue under the bulbar conjunctiva on the periphery of the bleb of case 1. The anatomical relationship between the holes and the avascular filtering bleb in case 2 was investigated using ultrasound biomicroscopy. RESULTS: In case 1, a biopsy showed the lacrimal gland tissue filtrated with mononuclear cells. In case 2, ultrasound biomicroscopy revealed no connection between the multiple leaking holes and localized filtering bleb. CONCLUSION: Following trabeculectomy at the superior temporal quadrant, we should consider downward extension of the lacrimal gland as a possible source of a patient's complaint of epiphora.

Relationship between the clinical efficacy of pentoxifylline treatment and elevation of serum T helper type 2 cytokine levels in patients with human T-lymphotropic virus type I-associated myelopathy.

OBJECT: Previously, we reported the efficacy of pentoxifylline (PTX) treatment in human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM). Here, we clarify the relationship between the clinical efficacy of PTX treatment and elevation of T helper type 2 (Th2) cytokine levels in HAM patients. PATIENTS AND METHODS: PTX (300 mg) was administered daily by the oral route to 12 HAM patients for 4 weeks. We assessed the relationship between the changes in neurological status (motor disability scores, the degree of spasticity on neurological examination, and the time required to walk 10 m) and the changes in serum and cerebrospinal fluid (CSF) levels of interferon-gamma (IFN-gamma) as a Th1 cytokine and interleukin-4 and -10 (IL-4 and -10) as Th2 cytokines measured by an EASIA (enzyme-amplified sensitivity immunoassay) kit. RESULTS: PTX treatment induced incremental increases in the levels of IL-4 and IL-10 in both sera and CSF of 6 HAM patients. Clinical improvement was associated with this elevation in IL-4 and IL-10. PTX treatment also induced a decrease in IFN-gamma levels in the sera of 6 HAM patients, but this was not correlated with clinical improvement. CONCLUSION: These results suggest that the correction of the immunological imbalance in Th1 to Th2 cytokine responses, with upregulation of IL-4 and IL-10, may account for the clinical improvement in HAM patients treated with PTX.

Plasmapheresis affects T helper type-1/T helper type-2 balance of circulating peripheral lymphocytes.

Plasmapheresis not only removes humoral factors, but may also modulate cellular immunity. We investigated whether plasmapheresis influenced T helper type-1/T helper type-2 (Th1/Th2) cytokine-producing-cell balance in 3 patients with neuroimmunological disease. The production of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and IL-4 in the culture supernatant of peripheral blood mononuclear cells stimulated by anti-CD3 and anti-CD28 was assayed. In 2 of 3 patients, plasmapheresis (immunoadsorption or plasma exchange) reduced Th1/Th2 cytokine ratio. The results may suggest that plasmapheresis induces a shift of Th1/Th2 balance in peripheral blood.