It is anticipated that availability of localized reference values for an extended range of peripheral blood lymphocyte phenotypes should supplement previously published reference values and enhance the utility of flow cytometric analysis undertaken in Switzerland.

Traumatic brain injury (TBI) induces local and systemic immunologic changes, release of cytokines, and cell activation. Perpetuation of these cascades may contribute to secondary damage to the brain. Therefore, the ability of the antiinflammatory mediator transforming growth factor-beta (TGF-beta) to downregulate intrathecal immunoactivation may be of fundamental value for diminishing the incidence and extent of secondary insults. In this study, the release of TGF-beta into cerebrospinal fluid (CSF) and serum of 22 patients with severe TBI was analyzed with respect to the function of the blood-brain barrier (BBB) for 21 days. Levels of TGF-beta in CSF increased to their maximum on the first day (median, 1.26 ng/mL), thereafter decreasing gradually over time. Median TGF-beta values in serum always remained within the reference interval (6.5 to 71.5 ng/mL). Daily assessment of the CSF-serum albumin quotient (QA) and of the CSF-serum TGF-beta quotient (QTGF-beta) showed a strong correlation between maximal QTGF-beta and QA, indicating a passage of this cytokine from the periphery to the intrathecal compartment across the BBB. However, calculation of the TGF-beta index (QTGF-beta/Q(A)) suggested a cerebral production of TGF-beta in 9 of 22 patients. Levels of TGF-beta could not be correlated with extent of initial injury by computed tomography (CT), CD4/CD8 ratios, acute lung injury, or clinical outcome as rated by the Glasgow Outcome Scale (GOS). Although increased levels of TGF-beta in CSF seem to parallel BBB function, a partial intrathecal production is suggested, possibly modulated by elevation of interleukin-6 (IL-6). Thus, TGF-beta may function as a factor in the complex cytokine network following TBI, acting as an antiinflammatory and neuroprotective mediator.

The chemokine monocyte chemoattractant protein (MCP)-1 is thought to be involved in breast carcinogenesis. We evaluated MCP-1 serum levels in patients with breast cancer (n = 135), ductal carcinoma in situ (DCIS) I–III (n = 30), benign breast lesions (n = 143) and in healthy women (n = 27). We determined the value of MCP-1 serum levels as a differentiation marker between malignant, preinvasive and benign breast diseases and as a predictive marker for the biological phenotype of breast carcinoma. Median (range) MCP-1 serum levels in patients with breast cancer, DCIS I–III, benign breast lesions and healthy women were 200 (57–692) pg/ml, 194 (58–525) pg/ml, 174 (39–529) pg/ml and 175 (67–425) pg/ml, respectively. No differences were ascertained between the patient groups. In patients with breast cancer, increased MCP-1 serum levels were correlated with advanced tumor stage (p = 0.04) and lymph node involvement (p = 0.04). We were not able to establish MCP-1 as a differentiation marker between malignant and benign breast diseases. Our data might indicate that MCP-1 influences breast carcinogenesis by facilitating tumor growth and metastatic spread, thus altering the biological phenotype of the disease.

Sezary syndrome (SS) is a leukemic variant of low-grade cutaneous T- cell lymphomas (CTCLs). The clonal T cells in this lymphoproliferative disorder are poorly characterized. Using antibodies against the variable region of the T-cell receptor (TCR V alpha/beta), we identified four predominant T-cell clones (two V beta 8+ clones, one V beta 5.1+, and one V alpha 2(a)+) in peripheral blood mononuclear cells (PBMC) of SS patients. Their phenotype was CD3+, CD4+, CD5+, CD45RO+. Clonal T cells were purified, and cytokine transcription and secretion was analyzed by reverse transcriptase-polymerase chain reaction (RT- PCR) followed by hybridization with biotinylated probes and enzyme- linked immunosorbent assays (ELISAs). The interleukin-10 (IL-10) PCR product was cloned and sequenced and found to be identical to the published cDNA sequence. The presence of accessory factor-1 (AF-1, or interferon-gamma [IFN-gamma] receptor beta-chain) encoding mRNA was assessed by RT-PCR and immunostaining using serum of rabbits immunized with the extracellular domain of a recombinant human AF-1 protein followed by APAAP staining. Clonal T cells transcribe and secrete mainly T-helper 2 cytokines (IL-10, -5, and -13). mRNA from purified SS clones but not mRNA from SS total PBMC was positive for AF-1 in an agarose gel and/or after hybridization. AF-1 transcription was associated with membrane-bound immunoreactivity for AF-1 in SS clones. SS-derived T-cell clones display T-helper 2 cytokines. This weakens cell-mediated immunosurveillance, and explains the clinical and immunologic abnormalities in SS patients. The T-helper 2 cytokine spectrum of all clones investigated is associated with overexpression of AF-1. This suggests that AF-1 is a potential marker for these clones (and eventually other T-helper 2 lymphocytes) and might represent a target for treatment of the disease.

Granuloma faciale (GF) is a rare, chronic skin disorder in which numerous treatment modalities have been used without any consistent long-term effect. We report three cases of GF, two of which were successfully treated with the Laserscope potassium-titanyl-phosphate 532-nm laser within 2 weeks and one with topical tacrolimus ointment 0.1%. Our observations suggest that these new treatment modalities for GF, which we report here for the first time, can provide effective and non-invasive treatment for this disease.