Travel to sunny countries is associated with changes in immunological parameters.

Under laboratory conditions, various studies have shown that changes in immunological parameters must be expected after exposure to ultraviolet (UV) light. The objective of the present study was to evaluate, whether such changes can also be revealed after a vacation to a sunny country without prior adaptation to ultraviolet radiation. In 32 volunteers white blood cells, lymphocyte subpopulations, sIL2-R, sCD14, immunoglobulins and complement factor C3 were determined before and after a vacation in a country with abundant sunshine during winter. The subjects received relevant doses of UVB as confirmed by questionnaires, UVB-dosimetry and the significant increase of 25-hydroxyvitamin D. After vacation, there was a significant decrease of the CD4/8 ratio and the serum concentration of IgG. The serum concentration of sIL2-R, sCD14, IgA and C3 was increased after the journey. Sunshine exposure without prior adaptation may be responsible for significant alterations in the immune system in association with a vacation during winter.

Effect of UVB plus tar therapy on serum levels of interleukin-2 receptors in patients with psoriasis.

Baseline serum levels of interleukin-2 receptor (IL2R) were measured in 65 patients with active psoriasis. IL2R levels in psoriatic patients were significantly higher than in healthy controls (582.4 +/- 289.23 u/ml vs. 369.64 +/- 111.10 u/ml; P less than 0.05), but did not differ statistically from values found in an atopic dermatitis control group (619.88 +/- 254.27 u/ml). Sex, age and severity of the disease do not affect levels of IL2R. The same IL2R levels were measured in 26 psoriatic patients receiving UVB plus tar therapy. This therapy, continued until clinical remission, lowered IL2R levels to values comparable to controls. This decrease may be due to an immunosuppressive effect of therapy.

Residual activation events functional after irradiation of mouse splenic lymphocytes.

The radioresistance of lymphocytes increases after mitogenic stimulation, suggesting that a radiosensitive activation event contributes to the overall radiosensitivity of lymphocytes. We have sought to identify this activation event by determining the extent of activation of mitogen-stimulated lymphocytes previously exposed to growth-inhibiting doses of radiation. Mouse splenic lymphocytes were exposed to 0-15 Gy 137Cs radiation, and structural and functional damage were assayed. Although damage to cellular thiols and nonprotein thiols was modest, there was a significant loss of viability by 6 h as determined by uptake of propidium iodide (PI). Since cells did not die immediately after irradiation, the activation events which remained were evaluated. Growth-inhibiting doses of radiation left cells partially responsive to mitogen, in that cells were able to exit G0 phase, but they could progress no further into the cell cycle than G1a phase. It is important to note that assessment of viability by uptake of PI indicated substantial cell death after 15 Gy (45%, 6 h; 90%, 24 h); however, cell cycle analysis at 24 h indicated no significant decrease in progression from G0 to G1a phase. The LPS-stimulated response of B cells was more radiosensitive than the Con A-stimulated response of T cells. Further analysis of the Con A response indicated that production of interleukin-2 (IL-2) was unaffected, but expression of the IL-2 receptor was inhibited. Inhibition of poly-ADP-ribosylation and damage to lipids did not prevent the lack of mitogen responsiveness, since neither the ADP-ribose transferase inhibitor 3-aminobenzamide nor lipid radical scavengers had restorative effects on the mitogenic response. Nor was Con A-stimulated incorporation of [3H]thymidine restored with inhibitors of prostaglandin or leukotriene synthesis, suggesting that inhibition was due to direct effects on the Con A responders, and not indirect effects mediated by arachidonate metabolites. These results indicate that growth-inhibiting doses of radiation trigger the process in lymphocytes that culminates in apoptosis, yet leave the cells partially responsive to mitogenic stimuli.

Serum soluble interleukin-2 (IL-2) receptor levels in women with breast carcinoma and its correlation with IL-2 receptor expression on blood lymphocytes and lymphocytic infiltration within the tumour.

This study describes serum levels of soluble interleukin-2 receptor (sIL-2R) in 13 healthy women, 10 women with breast dysplasia and 37 patients with breast carcinoma. A difference was found between sIL-2R levels in normal women and cancer patients. sIL-2R increased with the advance in stage of cancer but the extent of increase fell from stage III to stage IV as compared to the change from stage II to stage III. Of the 15 patients who were followed after surgery and/or therapy, 10 (67%) showed a fall in the serum sIL-2R levels. A negative correlation was found between sIL-2R levels and lymphocytic infiltration only within the malignant tissue. These findings probably indicate that sIL-2R exerts an immunomodulatory effect on blood lymphocytes by preventing their infiltration into the tumour tissue. To our knowledge, this is the first report of its kind in immunology of breast carcinoma.

Tumor necrosis factor-alpha activation of the IL-2 receptor-alpha gene involves the induction of kappa B-specific DNA binding proteins.

TNF-alpha induces the expression of IL-2R and promotes the proliferation and differentiation of T and B cells. In this report, we have studied the biochemical basis for TNF-alpha activation of the IL-2R alpha (Tac, p55) gene. Transfection of human T cell lines with selectively mutated forms of the IL-2R alpha promoter revealed that a kappa B element (nucleotides -267 to -256), as well as 5' flanking sequences (nucleotides -281 to -271) are required for TNF-alpha induction of this transcriptional unit. DNA binding studies demonstrated that this IL-2R alpha kappa B control element is specifically bound by a set of TNF-alpha inducible T cell nuclear proteins of relative Mr 80 to 90, 50 to 55, and 38 to 42 kDa. This protein recognition site from the IL-2R alpha promoter, as well as related kappa B motifs from the long terminal repeat of the type I human immunodeficiency virus, proved sufficient to impart TNF-alpha inducibility to an unresponsive heterologous promoter. These findings suggest that TNF-alpha-stimulated expression of the IL-2R alpha gene involves the induction of specific DNA binding proteins that in turn interact with a kappa B-like promoter element and facilitate activation of this transcription unit.

Anti-IL-2 receptor monoclonal antibody AMT-13 increases soluble IL-2 receptor levels in vivo.

A rat anti-interleukin-2 receptor (IL-2R) monoclonal antibody (mAb), AMT-13, has been shown to prolong cardiac allograft survival in mice. However, neither the mechanism of its immunosuppressive action, nor its other in vivo effects, have been studied extensively. We investigated the effect of AMT-13 on serum-soluble IL-2R levels by a quantitative ELISA technique. Following administration of multiple doses of AMT-13, sufficient to delay fetal pancreatic graft rejection, a rapid and lasting increase in soluble(s) IL-2R levels of up to 20-fold was observed. Levels returned to normal by Day 9 despite continued AMT-13 administration. A similar though less marked increase was observed following a single injection of AMT-13. Irradiation with 350 rads decreased sIL-2R levels, whilst rat Ig-treated control mice had sIL-2R levels within the normal range. In vivo administration of recombinant IL-2 also increased sIL-2R levels, but the effect was transient and slight. No effect on either the release of sIL-2R or expression of cell surface-associated IL-2 receptors was noted when splenocytes were cultured in the presence of AMT-13. We speculate that the increased concentration of sIL-2R in the serum of AMT-13-treated mice may play a role in the immunosuppressive action of this mAb.