Stimulation of soluble interleukin-2 release by tumor necrosis factor-alpha in cancer patients.
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Humans↗
Biomedical subjects
R Braczkowski
Publications and source records attributed to R Braczkowski.
Central injection of morphine stimulates plasma corticosterone and interleukin (IL)-6 and IL-6 R mRNAs in the pituitary and adrenals in adjuvant-induced arthritis.
Adjuvant-induced arthritis (AA) in the rat is a T-cell mediated, chronic inflammatory stress in which circulating interleukin (IL)-6 levels are elevated. In addition, there are profound neuroendocrine changes associated with the development of hind-paw inflammation which have major implications for the ability of the rat to respond the to stress. Central injection of morphine is also able to increase circulating IL-6 concentration in control animals. In the present study we have determined the effects of a single injection of morphine into the lateral ventricle of control and AA animals on plasma corticosterone levels, on changes in plasma corticosterone and on IL-6 and IL-6 receptor mRNAs in the pituitary and adrenal gland. IL-6 and IL-6 receptor mRNAs were increased in the anterior pituitary of AA rats given moprhine compared with saline-treated AA rats. In the adrenal cortex, IL-6 mRNA was unaltered and IL-6 receptor mRNA was significantly decreased under these same conditions. AA rats were unable to mount corticosterone response to acute stress but were able to respond to acute stimulation with e.g. LPS. In the present study we found a sustained increase in plasma corticosterone in control animals which was still significantly elevated 2 hours following morphine injection, with a further significant increase in AA rats. These data suggest that alternative systems distinct from those activated in response to acute stress are activated by morphine in the AA animals. The similarity with the sustained increase in corticosterone following LPS injection suggest that either similar pathways are involved, or that central opiates may be involved in mediating HPA axis response to stress.
Adrenal Glands↗
Decrease of erythropoietin level by human recombinant tumour necrosis factor alpha (hrec TNFalpha) in patients with advanced cancer.
UNLABELLED: Anaemia is a frequent complication of chronic inflammation, infectious diseases and cancer. Inappropriate erythropoietin production is regarded as one of the main causative factors responsible for the occurrence of anaemia. The pathogenesis of TNFalpha induced-anaemia has not been fully clarified yet and its influence on hematopoiesis has been suggested. We performed a clinical study to access the influence of hrec TNFalpha administration on plasma EPO concentration and the degree of anaemia in patients with advanced solid tumours for whom no other kind of therapy but palliative treatment was available. All these patients exposed mild anaemia (HT 36.1 +/- 1.0%). Plasma EPO was estimated at 8 a.m. before and after 5 days of TNFalpha therapy with a dose of 75 pg/day iv (cycle I). Two weeks later plasma EPO was estimated again before and after 5 days of TNFalpha administration of a double dose (150 microg/day) (cycle II). The control group comprised 8 non-cancer patients (5M/3F, age 48.5 +/- 6yr) with the same degree of anaemia (HT 36 +/- 1.1%) due to haemorrhage. In the control group the plasma EPO level was significantly higher (54.2 +/- 8 mU/ml) than in cancer patients before cycle I (17.1 +/- 2.5 mU/ml) and II (14.6 +/- 3.8 mU/ml) respectively.TNF administration was followed by a significant decline of plasma EPO both after the first (17.1 +/- 2.5 vs 9.0 +/- 1.5 mU/ml) and second cycle (14.6 +/- 3.8 vs 8.4 +/- 2.0 mU/ml) of TNF treatment. CONCLUSIONS: Patients with solid cancer and mild anaemia are characterised by inappropriate low plasma EPO concentration. Therapy with TNFalpha exerts a suppressive effect on EPO secretion in these patients.
Adult↗
Role of the pineal gland in the control of macrophage functions and its possible implication in cancer: a study of interactions between tumor necrosis factor-alpha and the pineal hormone melatonin.
Recent studies have shown the existence of reciprocal links between cytokine activity and immunomodulating neurohormones or neuropeptides. In particular, the pineal hormone melatonin (MLT) appears to influence IL-2 activity in cancer. The present study was performed to evaluate which interaction exists between MLT and another important cytokine, tumor necrosis factor-alpha (TNF), which is responsible for both antitumor cytolytic activity and cancer-related cachexia. In a first study, we analyzed MLT circadian rhythm under TNF administration (0.75 mg/day i.v. for 5 days) in 10 metastatic solid tumor patients. In a second study, we evaluated TNF serum levels in 10 metastatic solid tumor patients under therapy with MLT alone (20 mg/day orally in the evening for at least 1 month). In a third study, we have measured concomitantly daily serum levels of MLT and TNF in 30 patients with metastatic solid neoplasms. Nocturnal mean serum concentrations significantly increased in response to TNF injection. MLT therapy induced a significant decline in TNF mean values. Finally, patients with abnormally high MLT diurnal levels showed significantly lower TNF mean concentrations with respect to those with normal levels of the pineal hormone. This study, by showing the stimulatory effect of TNF on MLT secretion and the inhibitory action of MLT on TNF release, would suggest the existence of feed-back mechanisms operating between the pineal gland and TNF released from macrophages in human neoplasms.
Adult↗
[Treatment of advanced pancreatic cancer with interferon alpha, tumor necrosis factor and 5-fluorouracil (preliminary report].
This paper presents the first outcomes of a combined therapy of advanced cancer of pancreas with Interferon alpha, Tumor Necrosis and 5-Fluorouracil. Every subject underwent surgical treatment, but only in two cases partial resection was done. In the other subject only palliative operations were performed because of advances stages of neoplastic process. All patients were followed up during the time ranged between from 2.5-13.5 months. Complete remission was observed in one patient (survival time--9 months). In three subjects partial remission was reported, whereas in the left part of our cohort the general condition was steady. This research would be continued.
Adenocarcinoma↗