Chemo-immunotherapy in patients with metastatic melanoma using sequential treatment with dacarbazine and recombinant human interleukin-2: evaluation of hematologic and immunologic parameters and correlation with clinical response.

We have treated 18 patients with metastatic malignant melanoma (MM) with high-dose IL-2 administered by continuous iv infusion in combination with dacarbazine (DTIC), and correlated the clinical response with various hematologic and immunologic parameters. Two regimens differing in the sequence of treatment were employed, and 1-6 treatment cycles were given, depending on patient response. Two patients had a complete response (CR, 46+m, 14m), two patients a partial response (PR, 16m,6m), one a minimal response and four had a stable disease lasting 2-7 months, thus the response rate (CR+PR) was 22%. None of the following parameters, tested prior to initiation of the therapy and 1-2 days after termination of each course of IL-2, correlated with the clinical response: WBC counts (total and differential), levels of blood CD4 and CD8 T cells, NK cells, monocytes and B cells, production of IL-1 and IL-1 inhibitor by monocytes, responsiveness to 3 mitogens, NK/LAK cell activity, and serum levels of IL-1 alpha, IL-2, soluble IL-2 receptor, and TNF alpha. The only prognostic parameter was the greater increase in the level of IL-2 receptor (Tac)-bearing lymphocytes in the responding patients after 1-3 cycles of IL-2. The data suggests that non-specific immune parameters have no prognostic value for patients undergoing IL-2-based immunotherapy.

Serum levels of interleukin-2 receptor in ocular Behçet's disease.

Serum interleukin-2 receptor levels were evaluated in 69 patients who had chronic bilateral uveitis and in 22 control subjects. Fifty-one of the 69 patients with uveitis had the ocular type of Behçet's disease and 18 had pars planitis (intermediate uveitis). The mean serum interleukin-2 receptor level was 412.6 +/- 94.6 U/ml for the control group, 465.0 +/- 96.6 U/ml for the patients with intermediate uveitis, and 810.9 +/- 369.3 U/ml for those with ocular Behçet's disease. The serum interleukin-2 receptor levels of patients with ocular Behçet's disease were significantly different from the levels of both the control and the intermediate uveitis groups (P < .001). The differences in serum levels of patients with intermediate uveitis and the levels of the control subjects were not statistically significant. Treatment of patients with ocular Behçet's disease for four to six weeks with either cyclosporine, methylprednisolone, or a combination of both, decreased the intraocular inflammation in nearly all cases. The influence of treatment on the level of serum interleukin-2 receptor, however, was variable.

Levels of cytokines and collagen type I and type III as a function of age in human gingivitis.

The objective of this study was to examine the age-dependent relationships between levels of inflammatory cytokines and collagen in human gingival inflammation. The gingival biopsies were obtained from 142 patients, divided into the following age groups: 6 to 14 years (prepubertal children); 18 to 35 years (young adults); 36 to 54 years (mature adults); and 55 years or above. The patients were also divided according to the severity of gingivitis. The tissues were analyzed for the contents of the inflammatory cytokines interleukin (IL)-1 beta, IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) using specific ELISA kits, and interstitial collagen type I and type III using the ELISA method and specific antibodies. We found that in young adults, levels of IL-1 beta and IL-6 were significantly higher in inflamed than in non-inflamed gingiva. Total collagen in the young adults, however, was lower in inflamed than in non-inflamed gingiva. There was no significant difference in the levels of either IL-8 or TNF-alpha between inflamed and non-inflamed gingiva independent of age. No difference in the level of collagen type I between the inflamed and non-inflamed gingiva was found in any age groups. The level of collagen type III was lower in inflamed than in non-inflamed gingiva in both children and > or = 55 year group. The results indicate a disparity in the effect of age on the levels of cytokines and of collagen type I and type III in both clinically normal and inflamed gingiva.

The correlation between interleukin 2 and soluble interleukin 2 receptors to oestradiol, progesterone and testosterone levels in periovulatory follicles of in-vitro fertilization patients.

The present study was performed to evaluate the correlation between follicular fluid levels of interleukin 2 (IL-2) and IL-2 soluble receptor (sIL-2R), oestradiol, progesterone and testosterone levels, oocyte fertilization, embryo quality and pregnancy rates. Twenty-eight patients with a pure tubal factor and undergoing in-vitro fertilization and embryo transfer were randomly chosen and treated with gonadotrophin releasing hormone agonist (GnRHa) in the midluteal phase (long protocol) coupled with follicular phase administration of human menopausal gonadotrophin. Transvaginal follicular aspiration was performed 36 h after human chorionic gonadotrophin administration, followed 48 h later by embryo transfer. One hundred and twenty-three follicular fluids were sampled. The mean follicular fluid levels (+/- SD) were 2.30 +/- 0.80 fmol for IL-2, 458.2 +/- 236.0 units/ml for sIL-2R, 28.5 +/- 58.1 ng/ml for oestradiol, 2360.5 +/- 2846 ng/ml for progesterone and 7.22 +/- 7.08 ng/ml for testosterone. There was a significant (P less than 0.01) correlation between IL-2 and testosterone levels. No correlation was found between the lymphokines and serum oestradiol, follicular fluid progesterone, oocyte fertilization, embryo quality and pregnancy. It may be concluded that significant concentrations of IL-2 and sIL-2R exist in follicular fluid. Wide variations in follicular IL-2 and sIL-2R concentrations of different follicles were found in the same patients.