Immunotoxicological assessment of cyclosporin A by conventional pathological techniques and immune function testing in the rat

1997 ◽  
Vol 16 (2) ◽  
pp. 79-88 ◽  
Author(s):  
RWR Crevel ◽  
P. Buckley ◽  
JA Robinson ◽  
IJ Sanders

1 Groups of male rats were given different doses of cyclosporin A, ranging from the maximum tolerated dose (20 mg/kg/day) downwards, 7 days a week for 28 days using a protocol derived from OECD test guide line 407. 2 At the end of the test, one set of animals underwent a detailed necropsy and histopathological examination of lymphoid tissues. Immune function was assessed using the lymphoproliferative response and natural killer cell activity of their spleen cells. Another set of animals was immunised with sheep erythrocytes on day 25 and used to evaluate the ability to produce specific anti-sheep red blood cell antibody. 3 Cyclosporin A produced detectable effects on the immune system at all doses and at doses lower than other toxic effects. Both histopathological techniques and one of the immune function tests were able to identify changes at the lowest dose, 1.25 mg/kg/day. 4 The results of this investigation suggest that conven tional histopathological techniques, if applied to a range of lymphoid organs, are sufficient to identify potential immunotoxicants without recourse to im mune function tests.

2015 ◽  
Vol 114 (4) ◽  
pp. 586-595 ◽  
Author(s):  
Jelena Vulevic ◽  
Aleksandra Juric ◽  
Gemma E. Walton ◽  
Sandrine P. Claus ◽  
George Tzortzis ◽  
...  

It is recognised that ageing induces various changes to the human colonic microbiota. Most relevant is a reduction in bifidobacteria, which is a health-positive genus. Prebiotics, such as galacto-oligosaccharides (GOS), are dietary ingredients that selectively fortify beneficial gut microbial groups. Therefore, they have the potential to reverse the age-related decline in bifidobacteria and modulate associated health parameters. We assessed the effect of GOS mixture (Bimuno (B-GOS)) on gut microbiota, markers of immune function and metabolites in forty elderly (age 65–80 years) volunteers in a randomised, double-blind, placebo (maltodextrin)-controlled, cross-over study. The intervention periods consisted of 10 weeks with daily doses of 5·5 g/d with a 4-week washout period in between. Blood and faecal samples were collected for the analyses of faecal bacterial populations and immune and metabolic biomarkers. B-GOS consumption led to significant increases in bacteroides and bifidobacteria, the latter correlating with increased lactic acid in faecal waters. Higher IL-10, IL-8, natural killer cell activity and C-reactive protein and lower IL-1β were also observed. Administration of B-GOS to elderly volunteers may be useful in positively affecting the microbiota and some markers of immune function associated with ageing.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yong Ho Ku ◽  
Hyun Lee ◽  
Hwa Yeon Ryu ◽  
Jae Hui Kang

Abstract Background As the population of Korea ages, interest in healthcare has increased. In particular, there is an increasing demand for immune-function improvement to prevent infectious diseases. Phellinus linteus (PL) has previously been shown to exert immune-enhancing and anticancer effects. We aim to evaluate whether PL mycelium extract, cultured from the PL KCTC0399BP strain, can increase immune function, as measured using blood-test indicators. This clinical trial protocol is designed as the main trial and is based on the results of a pilot study. Methods This clinical trial is a randomized, double-blinded, placebo-controlled trial. Ninety-eight participants are enrolled and randomly divided into two groups: the experimental group (PL 1000 mg) and the control group (placebo). Participants are administered with experimental food or placebo for eight weeks. Blood tests are performed before trial initiation and 8 weeks later, at trial completion. Laboratory evaluation items are as follows: natural killer cell activity, tumor necrosis factor-α, interferon-γ, interleukin (IL)-1β, IL-2, IL-6, IL-12, immunoglobulin (Ig)G1, IgG2, and IgM. We will mainly use the full analysis dataset to statistically analyze the effectiveness of the treatment. Discussion This study evaluates the effects of PL extract on immune function and will contribute to knowledge on the value of PL as an immune-function–boosting functional food. Trial registration Clinical Research Information Service (CRIS) of Korea CRIS-KCT0005460. Registered on 12 October 2020


Foods ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 868
Author(s):  
Hee-Yeon Kwon ◽  
Sun-Il Choi ◽  
Xionggao Han ◽  
Xiao Men ◽  
Gill-Woong Jang ◽  
...  

The objective of the present study was to develop a concoction of natural products that could dramatically improve immune function with minimal possible side effects. Sasa quelpaertensis Nakai and Ficus erecta var. sieboldii are plants that are native to Jeju Island, Korea and are known to be rich in physiologically active substances. We prepared a mixture of different proportions and extraction conditions using two natural plants and determined their optimum mixing ratio and extraction method by assessing immune function-related biomarkers in RAW264.7 macrophages. Optimal extract (HR02/04(8:2)-W) was selected from in vitro experiments and its immunity-enhancing efficacy was evaluated in mice. After oral administration of extract to BALB/c mice for 2 weeks, nitric oxide production in the peritoneal exudate cells, natural killer cell cytotoxicity, cytokine expression in splenocytes, and total cell number of immune tissues and phenotype analysis were evaluated. Our results demonstrated that HR02/04(8:2)-W significantly enhanced the immune system by increasing natural killer cell activity, cytokine expression, and total number of cells in immune tissues. In conclusion, our study validates the role of HR02/04(8:2)-W in enhancing immunity and its potential development as a functional food.


2007 ◽  
Vol 35 (5) ◽  
pp. 626-636 ◽  
Author(s):  
W Zou ◽  
Q Guo ◽  
E Wang ◽  
J Cai ◽  
Z Cheng

Acute and chronic systemic administration of morphine is known to suppress immune function; however, the effect of chronic intrathecal (IT) morphine on immune function in inflammatory-induced pain is still unclear. This study examined the effects on the immune system of IT morphine in rats with formalin-induced pain. Lumbar IT catheters were implanted in rats and saline or 2.5, 5.0 or 10.0 μg/h morphine were administered for 7 days. On the last day, formalin-induced inflammatory pain was induced in rat hind paws and pain intensity was assessed. Rat spleens were then harvested for immune function assay. The IT morphine induced a dose-dependent analgesic effect and lactic acid dehydrogenase release assay showed dose-dependent suppression of natural killer cell activity. Concanavalin-A-induced splenocyte proliferation assay showed IT morphine to suppress T lymphocyte function in a dose-dependent manner. Flow cytometry showed IT morphine significantly to decrease T lymphocyte function and the percentages of T lymphocyte subsets in a dose-dependent manner. Hence, in inflammatory-induced pain IT morphine was found to suppress immune function. Chronic IT morphine should be used cautiously to treat chronic pain in immunocompromised cases.


2004 ◽  
Vol 29 (4) ◽  
pp. 419-443 ◽  
Author(s):  
Jennifer M. Dipenta ◽  
Julia Green-Johnson ◽  
René J.L. Murphy

Consistent reports of the positive relationship between regular physical activity and immunosenescence have generated much excitement in the field of exercise immunology. It is generally accepted that natural killer (NK) cell activity per NK cell decreases with age; decreases in NKCA have been associated with infection and death in the aged. The effects of exercise and training on natural killer cells, components of the innate immune system, have been studied extensively in young people. However, the published research on the elderly population is limited. Generally it has been found that training increases or does not change natural killer cell activity or counts in the elderly. The clinical relevance of these results is yet to be fully explored. In addition, the limitations of these studies on immune function have been many, and studies are often difficult to compare due to differences in their methods and presentation of results. Key words: aging, immune function, NKCA


1990 ◽  
Vol 68 (7) ◽  
pp. 1009-1016 ◽  
Author(s):  
James J. Pestka ◽  
Genevieve S. Bondy

Mycotoxins are a group of structurally diverse fungal secondary metabolites that elicit a wide spectrum of toxicologic effects. Of particular interest is the capacity of some mycotoxins to alter normal immune function when present in foods at levels below observable overt toxicity. Aflatoxin, patulin, citrinin, and zearalenone experimentally alter immunity, and recent evidence suggests that the immunologic effects of ochratoxin A and trichothecenes may have particular significance to human and animal health. For example, the capacity of ochratoxin A to inhibit natural killer cell activity and increase growth of transplantable tumour cells has been associated with renal and hepatic carcinomas in mice and might similarly contribute to human cancer. Impaired resistance to pathogenic microorganisms occurs after exposure to the trichothecenes T-2 toxin and vomitoxin. This may predispose food animals to infectious disease and could result in decreased productivity as well as increased animal-to-human transmission of pathogens such as Salmonella and Listeria. Vomitoxin also alters normal mucosal immune function, specifically at the level of regulation of development, differentiation, and homing of IgA-producing plasma cells. Interestingly, vomitoxin-induced enhancement of IgA production in the systemic compartment contributes to manifestations in the mouse that are highly analogous to human IgA nephropathy, the most common form of human glomerulonephritis worldwide. Over the long term, the extrapolation of mycotoxin-induced immunologic effects observed in inbred mice to actual disease in livestock and humans will require investigations that both simulate natural exposure conditions as well as improve understanding of the cellular and molecular bases for these effects among different species.Key words: mycotoxins, immunotoxicity, trichothecene, ochratoxin, aflatoxin.


2009 ◽  
Vol 11 (4) ◽  
pp. 351-362 ◽  
Author(s):  
Stephen J. Yermal ◽  
Linda Witek-Janusek ◽  
Jonna Peterson ◽  
Herbert L. Mathews

Prostate cancer is a leading malignancy in men, and prostatectomy is widely used for its treatment. Psychological distress and pain are commonly experienced in the perioperative period, and both can contribute to suppression of the immune response to cancer. This study evaluated perioperative pain, psychological distress, and immune function in men undergoing prostatectomy. Men were evaluated prior to surgery, 1 and 2 days postoperatively and 4—6 weeks postoperatively. Compared to cancer-free men, the prostatectomy group reported increased perceived stress, depression, confusion, and anxiety prior to surgery. During the 2 postoperative days, mood disturbance and anxiety persisted and were accompanied by mild elevations in pain and reduced vigor. At 4—6 weeks postoperative, mood, pain, and immune function were similar to those of the cancer-free group; however, the prostatectomy group continued to report significant elevations in anxiety. Natural killer cell activity (NKCA) was significantly reduced on Day 1 after prostatectomy, but by postoperative Day 2, NKCA returned to a level similar to that of the cancer-free group. The reduction in NKCA was not accompanied by changes in circulating immune cells, demonstrating that this reduction represented a functional change in NKCA. No correlations between immune variables and pain or psychological variables were found, suggesting that the postoperative reduction in NKCA was likely the result of the physical stress of the surgical experience. Suppression of immune defenses during the critical postoperative period can place cancer patients at risk for nascent tumor seeding. Additional interventions are needed to reduce this risk.


2001 ◽  
Vol 82 (12) ◽  
pp. 2889-2894 ◽  
Author(s):  
Beixing Liu ◽  
Isamu Mori ◽  
Md. Jaber Hossain ◽  
Li Dong ◽  
Yoshinobu Kimura

Peroral vaccination for preventing respiratory infectious diseases was investigated in a murine model using a temperature-sensitive (ts) mutant of parainfluenza virus type 1. The ts mutant virus administered perorally in drinking water neither multiplied nor caused lesions in the respiratory tract or the central nervous system. However, ts virus antigen-positive cells appeared in oropharyngeal lymphoid tissues. This type of antigenic stimulation was capable of inducing both humoral and cellular immune responses, together with an augmentation of interferon production and natural killer cell activity, making it possible to protect the mice against challenge infection with a virulent wild-type virus. These results suggest that the oral cavity, a constituent member of the common mucosal immune system, is a candidate organ applicable as a vaccine route against virus respiratory diseases.


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