G.S. Del Giacco

Medroxyprogesterone acetate reduces the in vitro production of cytokines and serotonin involved in anorexia/cachexia and emesis by peripheral blood mononuclear cells of cancer patients.

Medroxyprogesterone acetate (MPA) is widely used in oncology both in the treatment of hormone-related cancers and as supportive therapy in anorexia/cachexia syndrome (ACS), but conclusive data are not yet available to explain its anticachectic effect. ACS is characterised by weight loss, changes in metabolism, reduction of appetite, nausea and vomiting. Several cytokines, mainly interleukin (IL)-1, IL-2, IL-6 and tumour necrosis factor alpha (TNF alpha), are involved in the pathogenesis of ACS. Additionally, nausea and vomiting can be mediated by factors inducing serotonin (5-HT) production and/or release by pleiotropic cells including activated T lymphocytes. In the present study, we report the effect of MPA on peripheral blood mononuclear cells (PBMC) from 10 cancer patients in advanced stage of disease (6 head and neck, 2 colon, 1 lung and 1 ovary). The proliferative response of PBMC to PHA, anti-CD3 monoclonal antibody (MAb) or recombinant IL-2 (rIL-2), the production of IL-1 beta, IL-2, IL-6, TNF alpha and 5-HT by PHA-stimulated PBMC and the expression of lymphocyte membrane-bound IL-2 receptor (IL-2R) subunities (CD25 and CD122) were studied. The addition of MPA significantly reduced the PBMC proliferative response to PHA and anti-CD3 MAb but not to rIL-2. MPA 0.2 microgram/ml was also capable of reducing the levels of IL-1 beta, IL-6, TNF alpha and 5-HT produced in culture by PHA-stimulated PBMC, whereas it did not induce any change in the percentage of PBMC expressing either CD25 or CD122 or both molecules after stimulation with PHA or anti-CD3 mAb.

Megestrol acetate in neoplastic anorexia/cachexia: clinical evaluation and comparison with cytokine levels in patients with head and neck carcinoma treated with neoadjuvant chemotherapy

SummaryThe aim of our study (clinical phase II open pilot study) was to evaluate the toxicity of megestrol acetate and its ability to increase appetite and body weigth in patients with advanced-stage (III–IV) primary head and neck squamous cell carcinoma treated with neoadjuvant (primary) chemotherapy. Serum levels of interleukin-1α and β, interleukin-2 and 6, tumor necrosis factor-α, and the soluble receptor for interleukin-2 were evaluated before and after megestrol acetate treatment. The same cytokines and soluble interleukin-2 receptor were also measured in culture medium of peripheral blood lymphocytes from the same patients after stimulation with phytohemagglutinin. From April 1993 to February 1994, 11 male patients were enrolled in our study: their mean age was 57.8 years (range 43–69 years). Megestrol acetate was administered at a dose of 320 mg/day in the interval between chemotherapeutic cycles for a total of three consecutive cycles; 9 of the 11 patients could be evaluated (81.8%). Except for the performance status according to Karnofsky, all parameters were increased after megestrol acetate treatment. The average weight increased by 6.3 kg (13.2%), appetite by a score of 2.4 (38.6%) and the Spitzer’s quality of life index by a score of 2.4 (36.2%). The performance status according to Karnofsky decreased in only 1 patient, remained the same in most patients, and in 2 patients was slightly improved. No significant side effects were observed during treatment. Serum levels of interleukin-1α and β, interleukin-2 and 6, tumor necrosis factor-α, and soluble interleukin-2 receptor were significantly higher than in normal subjects, prior to treatment with megestrol acetate. These levels dropped after megestrol acetate treatment with a statistically significant decrease for interleukin-1α and β and tumor necrosis factor-α. There were no significant differences in the production of cytokines by peripheral blood lymphocytes stimulated with phytohemagglutinin from patients before megestrol acetate treatment and normal subjects, with the exception of interleukin-6 (higher in patients) and of soluble interleukin-2 receptor (lower in patients). There was no significant difference in the cytokines and soluble interleukin-2 receptor produced in culture before and after megestrol acetate treatment, except for interleukin-6 which decreased after treatment.

Allergy and sports

At the beginning of the third millennium, physicalexercise is often seen as a kind of panacea (a Greekword meaning ‘‘a cure for every sickness’’): there is nodoubt that it induces an increase in an individual’ssocialization and self-esteem, but it also has positivephysiologic and psychologic effects, improving thefunctioning of the cardiovascular, respiratory, andmuscular systems, and leading to modifications indiet. Sports competitions are now an important part ofeconomic, social, and cultural life, and leading athletesrepresent a model to be imitated by the majority ofyoung people and children. Thus, a large proportion ofthe young population practice exercise and sports inorder to achieve the best results from their bodies.Because allergic illnesses in industrialized countriesaffect 10–25% of the population (1), it may reasonablybe hypothesized that this percentage will be the same forathletes and amateurs of various sporting disciplines.Could it be that a well-trained amateur or aprofessional athlete faces some problems of apseudoallergic type when performing physical exercise?Or is it conceivable that an allergic subject can practicesports at the expert level and, indeed, become achampion?These issues will be examined in this review article.

Tumor-associated lymphocytes (TAL) are competent to produce higher levels of cytokines in neoplastic pleural and peritoneal effusions than those found in sera and are able to release into culture higher levels of IL-2 and IL-6 than those released by PBMC

This work was designed to study the proliferative response of tumor-associated lymphocytes (TAL) from neoplastic effusions against autologous tumor cells and the immunophenotype pattern of TAL from neoplastic effusions and that of PBMC of the same patients. We also compared the serum levels of the cytokines interleukin (IL) 1β, 2 and 6, tumor necrosis factor-α (TNFα) and soluble IL-2 receptor (sIL-2R) with those present in neoplastic effusions of the same patients. Moreover, we examined the ability of TAL and peripheral blood mononuclear cells (PBMC) to produce and release the cytokines and sIL-2R and to express membrane CD25 following their stimulation with phytohemagglutinin (PHA) in vitro. Finally, we compared the cytokines/sIL-2R production and membrane CD25 expression by PHA-stimulated PBMC of the patients with neoplastic effusions with a series of 90 cancer patients without neoplastic effusions and 20 normal healthy subjects. Thirteen neoplastic pleural and eight peritoneal effusions were collected from 11 patients with primary lung cancer, 7 with primary epithelial ovarian cancer, 1 with breast cancer, 1 with pleural mesothelioma, and 1 with pancreatic cancer. The proliferative response of TAL from neoplastic effusions against autologous tumor cells was lower than the response to PHA, IL-2, and anti-CD3, but significant. The percentage distribution of CD3+ and CD8+ lymphocyte subpopulations was higher in peritoneal than in pleural effusions, while the CD16+ subset was higher in pleural than in peritoneal effusions. The percentage distribution of CD16+ was significantly lower in pleural effusions than in PBMC of patients with pleural effusions. The CD39 antigen was higher on TAL from peritoneal effusions than on PBMC of the same patients. The levels of IL-1β and sIL-2R in peritoneal effusions did not differ from those measured in the sera of the same patients, while the levels of IL-2, IL-6, and TNFα were higher in the peritoneal effusions. The levels of IL-2, IL-6, TNFα, and sIL-2R, but not IL-1β, in pleural effusions were significantly higher than those found in the sera of the same patients. The amounts of IL-2 and IL-6 produced by TAL were generally higher than those released by PBMC. The secretion of cytokines IL-1α, IL-2, and sIL2R by PHA-stimulated PBMC was lower, but IL-1β and IL-6 secretion was higher in cancer patients with neoplastic effusions than in either cancer patients without neoplastic effusions or normal subjects. The CD25 expression on PHA-stimulated PBMC derived from cancer patients with neoplastic effusions was in the same range as that of cancer patients without neoplastic effusions and normal subjects. These findings suggest that TAL may be able to produce cytokines and may be amenable to immune manipulation.

Quantitative and functional abnormalities of total T lymphocytes in relatives of patients with Hodgkin's disease

Seven patients, long-term survivors of Hodgkins disease, and 24 of their relatives (parents, siblings and children), together with normal controls were studied for percentages, absolute counts and mitogen-proliferative responses by means of monoclonal antibodies, E rosette technique and in vitro cultures with PHA, ConA and PWM. The aim of the study was to ascertain whether the impaired cell-mediated immunity of Hodgkins patients was also present in relatives in order to elucidate the still debated etiology of the defect and of the disease (congenital? environmental? infectious?). The results show that both Hodgkins patients and their relatives have a significant decrease of total T cells (as T3+, T11+ and E rosette-forming cells) in peripheral blood and a significant impairment of polyclonal responses to all the mitogens employed. The Leu-7+ cells (i.e. a consistent amount of natural killer cells) are significantly increased only in the Hodgkins patients but not in their relatives. The T cell subpopulations (T4 and T8), B cells and monocytes do not show any difference between the patients, their relatives and normal controls. Our results seem to support, at least in part, the presence of a common defect of T cell lineage both in patients and in their relatives, but its etiology still remains uncertain (genetic? environmental?).

RAYNAUD'S PHENOMENON AND SCLERODERMA ASSOCIATED WITH SILICONE GEL BREAST IMPLANTS: AN EXAMPLE OF ASIA SYNDROME

Silicone-gel breast implants (SBI) have been widely used for breast augmentation. Although silicone is generally considered an inert substance, there has been much debate recently on its role in inducing chronic inflammation and systemic connective tissue diseases. The case of a young woman affected by Raynauds Phenomenon (RP), worsening of vitiligo and of autoimmune thyroiditis following SBI is reported in this paper. Removal of SBI led to temporary RP remission; however, despite notable clinical improvement, nailfold capillary microscopy showed progressive microcirculatory abnormalities consistent with a diagnosis of early scleroderma. Follow-up of the patient led to the diagnosis of Systemic Sclerosis (SSc) with pulmonary hypertension. The development of SSc after SBI is described, a condition that falls into the recently recognized “ASIA” (Autoimmune/inflammatory Syndrome Induced by Adjuvants) syndrome. Nailfold capillary microscopy is a valuable tool in early SSc diagnosis, in monitoring disease activity and in establishing the risk of an aggressive course of connective tissue disease following silicone breast implantation. The relationship between silicone and the immune system requires further reports and investigation in order to determine the main individual risk factors predisposing to the wide spectrum of adjuvant-induced responses.

Study of peripheral blood lymphocyte subset distribution and IL-2 receptor (IL-2 R) p55–p75 subunit expression in patients with cancer of different sites

The aim of the study was to evaluate the subset distribution and the IL-2 R p55–p75 subunit expression on unstimulated and phytohemagglutinin (PHA)-stimulated (at 3-d) peripheral blood mononuclear cells (PBMC), of patients with solid cancers of different sites. Indeed the expression of the two subunits of IL-2R is an essential prerequisite for The action of the IL-2 on CD8+, CD16+ lymphocytes as effectors in antitumor activity (LAK-cells). The subset distribution (CD3, CD4, CD8, CD16, DR) was assessed by cytofluorometry with specific monoclonal antibodies (MAbs); the p55 (CD25) and p75 subunit expression was evaluated by specific MAb (OKT26a and anti-p75). Ninety patients with advanced cancer (mainly non-small cell lung cancer [NSCLC], head and neck cancer, and gynecological cancer; mean age 55 yr; range 27–80) were studied. Thirty-five age- and sex-matched healthy subjects were studied as controls. Our data show that there is no significant difference in the subset distribution between cancer patients and controls. Furthermore, no difference has been found in the expression of p55 subunits on unstimulated PBMC between cancer patients and controls. No difference has been found in the expression of both p55 and p75 subunits on PHA-stimulated PBMC between cancer patients and controls. Our results can support the rationale for further clinical trials with IL-2 in solid malignancies.

Primary (neoadjuvant) combined modality therapy in the management of locally advanced squamous cell carcinoma of the head and neck

Recently, a combined modality therapy, usually chemotherapy (Neo-Adjuvant chemotherapy) followed by radiation therapy has been tested as an approach to sparing major surgery in patients with locally advanced head and neck cancer. Current choices for such patients include 1) a complete surgical resection with either preoperative or postoperative radiation therapy, 2) a Neo-Adjuvant chemotherapy followed by surgery and postoperative radiation therapy, or 3) a Neo-Adjuvant chemotherapy plus radiation therapy, and surgery if disease recurs [1].

The Present Status of Clinical Use of Levamisole

Levamisole (LMS) is the levorotatory isomer of Tetramisole, whose potent antihelminthic activity has been known since 1966.1 In 1971 Renoux and Renoux2 found that LMS could potentiate immunity in mice.

Exercise-Induced Asthma: An Update

Exercise-induced asthma (E.I.A) affects 12–16% of the general population and most of the patients affected by extrinsic or intrinsic asthma. Surprisingly, also a high percentage of professional and Olympic athletes are affected, showing that E.I.A. does not impair physical activity, whereas endurance sports bear a higher risk than the others. The mast cell role, late asthmatic responses, diagnosis, therapy, theories and data about immunological parameters in sports are taken into consideration in this review.