Sulphasalazine and Derivatives, Natural Killer Activity and Ulcerative Colitis

1985 ◽  
Vol 69 (2) ◽  
pp. 177-184 ◽  
Author(s):  
P. R. Gibson ◽  
D. P. Jewell
Keyword(s):  
Ulcerative Colitis ◽  
Natural Killer ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Nk Activity ◽  
Aminosalicylic Acid ◽  
Lipoxygenase Inhibitor ◽  
Peripheral Blood Mononuclear ◽  
Killer Activity

1. The effects of sulphasalazine, 5-aminosalicylic acid (5-ASA), sulphapyridine and azodisalicylic acid (ADS) in vitro on the natural killer (NK) activity of peripheral blood mononuclear cells (MNC) have been examined and compared with those of the lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA) and the cyclooxygenase inhibitor, indomethacin. 2. Sulphasalazine, sulphapyridine and ADS inhibited NK activity with 50% inhibitory concentrations (IC50) of 0.7, 2.5 and 4.0 mmol/l respectively. The effect was rapidly reversible. In contrast, 5-ASA minimally inhibited NK activity at 50 mmol/l only. 3. NDGA potently inhibited NK activity (IC50 27 μmol/l) but this was only partly reversible in short term incubations. Indomethacin had no effect at concentrations less than those inhibiting cyclo-oxygenase activity (1-10 μmol/l) but potently and reversibly inhibited NK activity at or above 25 μmol/l. 4. The inhibitory effects observed were unlikely to be due to direct toxicity of effector cells as 5-ASA, sulphapyridine and ADS had no effect on the viability of peripheral blood MNC, whereas NDGA and indomethacin lysed MNC only at maximal concentrations tested. Though sulphasalazine produced MNC lysis at and above 1 mmol/l, the rapid reversibility of the inhibition of NK activity at 1 mmol/l suggested that lysis of NK cells contributed little to the suppressive effect at this concentration. 5. The disparity of the therapeutic efficacy and effects on NK activity of sulphasalazine and its derivatives in vitro may suggest that NK activity is not a major pathogenic mechanism in ulcerative colitis. Any inhibitory effect on cellular immune function of indomethacin does not necessarily reflect an effect of cyclo-oxygenase inhibition.

Impaired natural killer cytotoxicity in peripheral blood mononuclear cells in Graves' disease

1995 ◽  
Vol 132 (2) ◽  
pp. 175-180 ◽  
Author(s):  
Mónica Marazuela ◽  
Juan A Vargas ◽  
Melchor Alvarez-Mon ◽  
Fernando Albarrán ◽  
Tomás Lucas ◽  
...  
Keyword(s):  
Natural Killer ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Natural Killer Activity ◽  
Graves Disease ◽  
Nk Activity ◽  
Peripheral Blood Mononuclear ◽  
Killer Activity ◽  
Blood Mononuclear Cells

Marazuela M, Vargas JA, Alvarez-Mon M, Albarrán F, Lucas T, Durántez A. Impaired natural killer cytotoxicity in peripheral blood mononuclear cells in Graves' disease. Eur J Endocrinol 1995;132:175–80. ISSN 0804–4643 We studied the natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) in patients with Graves' disease (GD). Peripheral blood mononuclear cells from 20 untreated hyperthyroid patients with GD showed a significantly reduced NK activity against 51 Cr-labeled K562 cells (33.9 ± 15.9%), while in 32 euthyroid patients under antithyroid drug therapy, NK activity was similar to that of controls (46.9 ± 17.3 and 49.9 ± 20.2%, respectively). Furthermore, normalization of thyroid function with antithyroid drugs was associated with a significant increase and normalization of NK activity during the follow-up of nine GD patients (from 29.2 ± 17.9 to 48.1 ± 16.5%). This phenomenon could not be ascribed to a defective number of NK cells because the amounts of CD56 + and CD16 + cells in PBMC from both hyperthyroid and euthyroid GD patients were within normal ranges. Natural killer activity of PBMC from patients with toxic multinodular goiter was similar to that of normal controls (45 ± 12.8 to 49.9 ± 20%). No correlation was found between natural killer activity and serum levels of free thyroxine, TSH-inhibitory immunoglobulins, thyroidal antibodies to thryoglobulin and thyroidal microsomal antigen, dose or duration of antithyroid drug therapy. Natural killer activity from both controls and GD patients was enhanced in vitro by addition of recombinant interleukin 2 (IL-2), reaching control levels in hyperthyroid patients. These abnormalities were not associated with a defective IL-2 production by T cells, nor with a decreased IL-2R expression. We conclude that in untreated Graves' disease there is a decrease in NK cell activity in PBMC, probably dependent on the autoimmune process. Possible biological and clinical implications are discussed. Monica Marazuela, Hospital de la Princesa, c/Diego de Léon 62, Madrid 28006, Spain

scholarly journals Cytotoxic Activity of Peripheral Blood Mononuclear Leukocytes, Activated by Interleukin-2/β-Cyclodextrin Nanocomposition against Androgen Receptor-Negative Prostate Cancers

ISRN Oncology ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-7
Author(s):  
Natalia Yu. Anisimova ◽  
Andrey V. Sosnov ◽  
Nadezhda E. Ustyuzhanina ◽  
Gianfranco Baronzio ◽  
Mikhail V. Kiselevsky
Keyword(s):  
Peripheral Blood ◽  
Water Solubility ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Natural Killer Activity ◽  
Mononuclear Leukocytes ◽  
Peripheral Blood Mononuclear ◽  
Killer Activity ◽  
K 562 Cells

Nanocomposition comprised of interleukin-2 in suboptimal noneffective concentration and β-cyclodextrin was studied in vitro. This preparation as well as interleukin-2 in optimal concentration was shown to increase natural killer activity to K-562 cells and cytotoxicity of activated peripheral blood mononuclear cells (PBMCs) against PC-3 and DU 145 cells. At the same time β-cyclodextrin or interleukin-2 in equimolar concentrations did not influence the spontaneous killer activity of PBMC. This combination of cyclodextrin + interleukin-2 led to the decrease of interleukin-2 effective concentration by an order. This phenomenon could be explained by cyclodextrins ability to promote the formation of nanoparticles with drugs, which results in enhancing their water solubility and bioavailability. Besides, interleukine-2/β-cyclodextrin nanocomposition as opposed to interleukin-2 alone led to increasing the number of not only lymphocytes, but also macrophages contained in activated PBMC population. Application of low concentration of interleukin-2 allowing for good clinical efficiency may significantly mitigate the side effects of the drug and enable to develop adoption of immunotherapy for patients with androgen-resistant prostate cancer.

scholarly journals Autologous Enhancement by Interferon of Natural Killer Activity of Human Peripheral Blood Lymphocytes

1994 ◽  
Vol 3 (5) ◽  
pp. 341-346
Author(s):  
S. B. Cheknev ◽  
Y. G. Ashmanova ◽  
A. D. Pritsker ◽  
O. L. Latysheva ◽  
F. I. Yershov ◽  
...  
Keyword(s):  
Natural Killer ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Nk Activity ◽  
Killer Activity ◽  
Blood Lymphocytes ◽  
Healthy Donors ◽  
Ifn Γ

Thein vitroaction of interferon (IFN)-α and IFN-γ from six healthy donors and ten patients with multiple sclerosis (MS) on natural killer (INK) activity of peripheral blood lymphocytes (PBL) was studied in an autologous system. The NK activity of PBL was detected by a cytotoxic test using3H-uridine human erythromyeloblast K562 cells. Autologous IFN-α and IFN-γ did not augment NK activity of PBL from healthy donorsin vitro, whereas in samples from MS patients the IFNs strongly stimulated NK cell cytotoxic function. This stimulation suggests the existence of an inhibitor of regulatory IFN action, that is produced in healthy donors simultaneously with IFN in response to IFN induction, but which is lacking in commercial IFN preparations. The factor-containing supernatants from healthy donors reduced the stimulatory action of autologous IFNs in patients with MS almost until complete blockade. Because this inhibitor was absent in patients with MS, deficiency of an inhibitor of IFN regulatory action in MS could open the way to treatment of this compartment of the immune system.

scholarly journals Compensatory effect of TNFalpha on low natural killer activity in the elderly.

2000 ◽  
Vol 47 (2) ◽  
pp. 301-311 ◽  
Author(s):  
J Myśliwska ◽  
E Bryl ◽  
P Trzonkowski ◽  
A Myśliwski
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Natural Killer Activity ◽  
The Elderly ◽  
Nk Activity ◽  
Killer Activity ◽  
Healthy Elderly

Regulatory effect of CD25, an activation antigen the alpha subunit of interleukin 2 receptor (IL2R) on the activity of natural killer (NK) cells was studied in fifty elderly (57-70 years old) and fifty young people (19-35 years old). Cytotoxic NK activity was assessed by 51Cr release assay, the levels of interleukin 2 (IL2) and tumour necrosis factors alpha (TNFalpha) were measured using bioassays and expression of CD16 and CD25 proteins by flow cytometry. Low NK activity in the elderly was associated with decline of full health, lowered serum concentration of IL2 and increased production of TNFalpha during NK reaction. Inhibition of TNFalpha activity by anti-TNF monoclonal antibody suppressed exclusively NK activity of low NK responders. Moreover, stimulation in vitro of blood mononuclear cells, with TNFalpha induced in the elderly low NK responders a significantly higher increase of the CD25 expression on the surface of NK cells as compared with that in the elderly high responders. Since the CD25 molecule constitutes a subunit of the high affinity receptor, binding IL2 to immunocompetent cells, its increased expression on NK cells of low NK responders would enable them to bind even low amounts of the endogenous IL2 available in this group of the elderly. Thus, an overproduction of TNFalpha seems to be a mechanism compensating, in the non-fully healthy elderly, for the decreased IL2 production, promoting efficient cytotoxic reaction.

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