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PubMedDate not supplied

Effects of soman on neuroendocrine and immune function.

We have previously reported that plasma growth hormone (GH) and prolactin levels were markedly decreased in rats two weeks following a single dose (100 micrograms/kg, SC) of soman. We have now conducted additional experiments to attempt to determine whether neuroendocrine responses to physiological or pharmacological challenge are altered in rat survivors of soman exposure, and whether immune function, which can be affected by circulating hormones, is altered in the soman-exposed rats. In the present study, basal prolactin levels were not significantly lower in the soman-treated rats although prolactin increases in response to physiological or pharmacological challenge were attenuated. Also, basal growth hormone levels in soman survivors were similar to control levels in 2 of 3 experiments in the present report. In the third experiment, growth hormone levels were lower in soman-treated animals. Endocrine abnormalities appeared to be related to the severity of soman insult as assessed by changes in body weight following exposure. Both ACTH and prolactin responses to stress were impaired in a severely affected subpopulation of soman survivors. The thymus, an important immune organ, was decreased in weight in severely affected soman survivors, but other tests of immune function did not show differences between control and soman-exposed rats.

Adrenocorticotropic Hormone↗
PubMed1987

Analysis of Epstein-Barr virus-specific and non-specific immune functions in a patient during the development of a non-Hodgkin's lymphoma.

A 57-year-old woman who presented with a reactive non-malignant lymphadenopathy was observed subsequently during the development of a nodular centroblastic non-Hodgkin's B-cell lymphoma. The Epstein-Barr virus (EBV)-specific antibody profile and EBV-specific and non-specific cell-mediated immune functions were determined at first presentation, and at various times during progression, in order to determine whether EBV was causally involved in the lymphoma and to assess in general the patient's cell-mediated immune function. At presentation, an immunodeficient status was suggested by an EBV-specific antibody profile indicative of an activated persistent infection; high antibody titers to viral capsid antigen (VCA) and early antigens (EA), but a low level of antibodies to EBV nuclear antigen (EBNA) confirmed by lack of leukocyte migration inhibition in response to EBNA (LMI-EBNA). The number of positive cells reactive with OKIa1 monoclonal antibody was significantly depressed, as was also the natural and interferon-activated killing (NK-IAK). After emergence of the lymphoma, NK-IAK reactivity and spontaneous lymphocyte DNA synthesis augmented in parallel with an increase in the frequency of Leu-7+ blood lymphocytes. The EBV-specific cell-mediated response, reflected by the outgrowth inhibition (OI) test was abolished in parallel with a decrease in the frequency of OKT3- and OKT4-positive lymphocytes.

Cell Migration Inhibition↗
PubMed1998

Effect of zinc supplementation on the morbidity, immune function, and growth of low-birth-weight, full-term infants in northeast Brazil.

In Brazil, the highest incidence of low birth weight (LBW) occurs in the northeast, and diarrhea and respiratory infections are the main causes of infant mortality and morbidity. We hypothesized that LBW infants may be zinc deficient, and that this might be adversely affecting their immune function, morbidity, and postnatal growth. We therefore examined the effect of zinc supplementation on these outcomes during the first 6 mo of life. LBW full-term infants (mean birth weight 2337 g) were given daily for 8 wk either 5 mg Zn (n = 71), 1 mg Zn (n = 68), or a placebo (n = 66). Morbidity was determined prospectively through daily home visits (except on Sunday) during weeks 0-8, then twice weekly in weeks 9-26. Anthropometric measurements were made at 0, 4, 8, 17, and 26 wk. Immune function was assessed at 8 wk by the phytohemagglutinin skin test. Supplementation (5 mg Zn) was associated with a 28% reduction in diarrhea prevalence over the 6-mo period [after adjustment for confounders (P = 0.043)], and a 33% reduction in the prevalence of cough (NS, adjusted prevalence P = 0.073). All infants had a positive immune response at 8 wk. Although supplementation had no significant effect on weight and length gains from 0 to 26 wk, infants given 5 mg Zn gained more weight than infants given placebo during weeks 17-26 (P = 0.024, analysis of variance). There was no effect on any outcome with 1 mg Zn. We conclude that 5 mg Zn/d is of benefit to LBW, full-term infants who only have a modest weight deficit.

Cough↗
PubMed2003

Effects of ganopoly (a Ganoderma lucidum polysaccharide extract) on the immune functions in advanced-stage cancer patients.

Preclinical studies have established that the Ganoderma lucidum polysaccharide (GLPS) fractions have potent anti-tumor activity, which has been associated with the immuno-stimulating effects of GLPS. However, it is unclear whether GLPS has immuno-modulating effects in humans in vivo. This study aimed to investigate the effects of Ganopoly, the polysaccharides fractions extracted from G. lucidum, on the immune function of advanced-stage cancer patients. Thirty-four advance-stage cancer patients were entered onto this study, and treated with 1800 mg Ganopoly, three times daily orally before meals for 12 weeks. Immune parameters (cytokines, T cell subsets, mitotic response to phytohemagglutinin (PHA) and natural killer activity) were compared between baseline and after 12-week treatment. Thirty patients are assessable for their immune functions. Treatment of Ganopoly for 12 weeks resulted in a significant (P < 0.05) increase in the mean plasma concentrations of interleukin (IL-2), IL-6, and interferon (IFN)-gamma, whereas the levels of IL-1 and tumor necrosis factor (TNF-alpha) were significantly (P < 0.05) decreased. A marked variability among patients with advanced-stage cancer was observed in the numbers of each lymphocyte subset at baseline. The mean absolute number of CD56+ cells was significantly (P < 0.05) increased after 12-week treatment of Ganopoly, whereas the numbers of CD3+, CD4+, and CD8+ were just marginally increased compared to baseline levels, with the CD4:CD8 T cell ratios unchanged. PHA responses after 12-week treatment with Ganopoly were enhanced in most patients, when compared to pretreatment baselines (P < 0.05). In addition, Ganopoly treatment resulted in a significant increase (P < 0.05) in the mean NK activity compared to baselines (34.5 +/- 11.8% vs 26.6 +/- 8.3%). The present study indicates that Ganopoly enhanced the immune responses in patients with advanced-stage cancer. Clinical evaluations of response and toxicity are ongoing.

Adult↗
PubMed2004

Epstein-Barr virus-encoded dUTPase modulates immune function and induces sickness behavior in mice.

Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis (IM). In addition, latent infections with EBV are associated with nasopharyngeal carcinoma (NPC) and Burkitt's Lymphoma (BL). Antibodies to several EBV-encoded early antigens (EA) are often observed in patients with NPC and BL, however, the role of EBV-encoded proteins in the etiology of these and other EBV-associated diseases is not completely understood. The EA complex encodes for at least six different viral enzymes including deoxyuridine triphosphate nucleotidohydrolase (dUTPase). dUTPase has recently been shown to modulate activation of human peripheral blood mononuclear cells in vitro (unpublished data). Therefore, these studies were designed to test whether dUTPase would modulate immune function in an in vivo model. Mice were injected with purified EBV dUTPase, and baseline immune function and sickness behaviors were measured. EBV dUTPase treatment inhibited replication of mitogen-stimulated lymphocytes obtained from treated mice. These lymphocytes were also less able to synthesize interferon-gamma after re-stimulation. In addition, treatment with dUTPase induced sickness behaviors. For example, as compared to control animals, dUTPase-treated animals lost body mass, had elevated body temperature, and displayed diminished locomotor activity. These data suggest that individual viral proteins may play a role in the pathophysiology of EBV associated disease.

Animals↗
PubMed1993

Effects of retroviral infections on immune function in African-American intravenous drug users.

OBJECTIVES: To determine the effect of retrovirus infection and co-infection, and intravenous substance use, on immune function in African-Americans. DESIGN: A cohort of South Florida street-recruited African-American intravenous drug users formed the study population. The cohort consisted of 90 HIV-negative & human T-lymphotropic virus (HTLV)-negative, one HIV-negative & HTLV-I-positive, 11 HIV-negative & HTLV-II-positive, 79 HIV-positive & HTLV-negative, one HIV-positive & HTLV-I-positive and 21 HIV-positive & HTLV-II-positive individuals. The results reported are for the cross-sectional, baseline assessment of immune parameters. METHODS: Lymphocyte phenotypic distributions and functional markers, including proliferative response to mitogens and natural killer cell cytotoxicity, were determined. Serum immunoglobulin (Ig) levels were determined as a measure of B-cell activity. RESULTS: HTLV-II infection was associated with increases in CD8 lymphocyte count and serum Ig, but with no other significant immunologic changes. The distribution of CD4 and CD8 percentages, CD4:CD8 ratio, phytohemagglutinin (PHA) and pokeweed mitogen (PWM) reactivity, IgA and IgG for the four retrovirus serostatus groups suggested the possibility of interactive effects in the co-infected group, as demonstrated by a trend toward lower medians for CD4 and for PHA and PWM response and higher medians for IgG, IgA and CD8. Retrovirus-seronegative intravenous drug users had significantly impaired immune status compared with non-drug-using control individuals. CONCLUSIONS: Immunologic dysfunction attributable to HTLV-II infection was minor compared with HIV infection in this population. Study subjects who were co-infected with HIV and HTLV demonstrated more impairment of immune function than individuals with single retrovirus infections.

Adult↗
PubMed2002

Status incongruity in Samoan youth: a biocultural analysis of culture change, stress, and immune function.

In Samoa, the presence of a matai title in the family has historically been a valued source of social status. However, as the process of Westernization continues, new sources of social status are emerging. This study explores the degree to which new and old markers of social status agree--or disagree--and the consequences they have for the experience of stress in 329 Samoan adolescents. The study integrates cultural and biological methods and data, and measures an aspect of immune function (antibodies against the Epstein-Barr virus) as a biomarker of psychosocial stress. Results indicate that status "incongruent" adolescents experience significantly more stress (indicated by reduced immune function), and that emerging markers of social status are becoming inextricably linked to "traditional" markers in such a way that discordance between them is a significant source of stress. This study proposes new conceptual models for future studies of culture change and suggests that biomarkers may represent ethnographic tools that can provide insight into hidden cultural dynamics and the experience of stress.

Acculturation↗
PubMed1976

Lymphocyte transformation in human plasma without addition of synthetic medium. A study of immune function in patients with chronic uraemia or diabetes mellitus.

The in vitro response of lymphocytes obtained from normal subjects, uraemic patients on haemodialysis and diabetic patients was studied using cultures containing either medium plus plasma (medium cultures) or plasma alone (plasma cultures). The study demonstrated that plasma alone can adequately support lymphocyte transformation induced by nonspecific mitogens (PHA and PWM) and allogeneic lymphocytes in mixed lymphocyte culture (MLC) reaction. This investigation further confirms our previously reported findings that uraemic patients undergoing haemodialysis have a normal lymphocyte response in MLC and to PHA and PWM. Plasma cultures give results similar to conventional medium cultures in subjects where lymphocyte transformation is normal. The lymphocyte hyporactivity observed in diabetics is, however, better shown in the plasma cultures. The suppressed response of the diabetic patient's lymphocytes to PHA and PWM both in the presence of autologous and normal AB plasma suggests intrinsic lymphocyte dysfunction as the explanation for impaired immune function. Plasma cultures may provide a better in vitro system for the evaluation of immune function in certain groups of patients where it is desirable to distinguish between intrinsic abnormalities of lymphocyte function and the effect of humoral immunosuppressive factors.

Adult↗
PubMed1998

Small volumes of enteral feedings normalise immune function in infants receiving parenteral nutrition.

BACKGROUND/PURPOSE: Parenteral nutrition (PN) is associated with a risk of septicaemia. This may be caused by impairment of immune function related to PN. The authors investigated the effects of the addition of enteral feedings to PN on the immune status of human newborn infants. METHODS: Ten surgical infants (age less than 6 months) requiring PN were studied in two consecutive phases: (A) after 31.1+/-6.0 days (mean +/- SEM) of PN with no enteral feeding (total PN); and (B) after 4.7+/-1.1 days from the addition of small volumes of enteral feeding to PN. Full blood count and liver function tests were not significantly different between phases A and B. A control group (n = 9) of infants receiving a normal enteral diet was also studied. Host bactericidal activity against coagulase-negative staphylococci (CNS) was measured by an in vitro whole blood model. Bacterial killing was measured after a 45-minute bacterial challenge using the Miles-Misra technique. Tumour necrosis factor-alpha (TNF-alpha) was measured by enzyme-linked immunosorbent assay (ELISA) after 2 hours of bacterial challenge. RESULTS: The lowest level of CNS killing (37.7+/-5.2%), was observed in patients receiving total PN. This increased significantly after the addition of small enteral feeds (52.0+/-4.6%, P < .005) approaching the levels measured in controls (65.1+/-3.4%). TNF-alpha production was low during total PN (1467+/-297 pg/mL) and rose significantly after the addition of minimal enteral feeds (4,661+/-1,311 pg/mL, P < .05). The increase in CNS killing after the addition of small enteral feeds in patients on PN was significantly correlated with the duration of enteral feeding (r = 0.8, P = .006). CONCLUSIONS: These results indicate that the introduction of small volumes of enteral feed improve the impaired killing of CNS and the abnormal cytokine response observed during total PN. This implies that stimulation of the gastrointestinal tract may modulate immune function in neonates and prevent bacterial infection.

Bacteremia↗
PubMed2005

Effects of Maharishi Amrit Kalash 5 as an Ayurvedic herbal food supplement on immune functions in aged mice.

BACKGROUND: Maharishi Amrit Kalash (MAK) 5, one of the Ayurvedic food supplements, belongs to a group of substances known as Rasayana. MAK5 and other Rasayanas are believed to enhance the body's resistance to infections and disease, and enhance longevity. In this study, we determined the effects of administration of MAK5, one of the Ayurvedic food supplements on immune functions in young and old mice. METHODS: Male C3H/He N mice were divided into five groups: two no treatment groups (old control: 22-month-old and young control: 2-month-old) and three MAK5 treated groups with differing dose of MAK5. MAK5 was given p.o. at 50 mg/kg, 100 mg/kg or 200 mg/kg per day (3 days/week) for 2 months. RESULTS: We found that glucose consumption of peritoneal macrophages from old mice treated with MAK5 at all doses and incubated for 48 and 72 h were significantly greater than that in the control group. Nitric oxide production of peritoneal macrophages stimulated by lipopolysaccharide (LPS) in old mice treated with MAK5 at all doses was significantly greater than that in the old control group, but not compared to the young control group. Stimulation index (S.I.) in old mice gavaged with MAK5 at all doses was significantly higher than that in the old control group. IL-2 production stimulated by Con A in old mice given MAK5 at all doses was significantly higher than that in the old control group. Production of IFN-gamma stimulated by Con A in old mice given MAK5 at doses of 100 mg/kg and 200 mg/kg were significantly higher than that in the old control group. IL-4 production of splenic lymphocyte stimulated by Con A in old mice given MAK5 at dose levels of 100 and 200 mg/kg were significantly higher than that in the old control group. CONCLUSION: The results suggest that MAK5 suppressed the age associated glucose consumption of peritoneal macrophages and cellular immune function reduction, and that it contributes to the prevention of the immunosenescence.

Administration, Oral↗
PubMed2004

Long-term high copper intake: effects on indexes of copper status, antioxidant status, and immune function in young men.

BACKGROUND: Short-term high copper intake does not appear to affect indexes of copper status or functions related to copper status, but the effects of long-term high copper intake are unknown. OBJECTIVE: A study was conducted in men to determine the effect of long-term high copper intake on indexes of copper status, oxidant damage, and immune function. DESIGN: Nine men were confined to a metabolic research unit (MRU) for 18 d and were fed a 3-d rotating menu providing an average of 1.6 mg Cu/d. The men continued the study under free-living conditions for 129 d and supplemented their usual diets with 7 mg Cu/d. The men then returned to the MRU for 18 d of the same diet as during the first period, except that copper intake was 7.8 mg/d. Plasma copper, ceruloplasmin activity, ceruloplasmin protein, plasma malondialdehyde, benzylamine oxidase activity, erythrocyte superoxide dismutase, hair copper, urinary copper, and urinary thiobarbituric acid-reactive substances were measured during each MRU period. RESULTS: Ceruloplasmin activity, benzylamine oxidase, and superoxide dismutase were significantly higher at the end of the second MRU period than at the end of the first. Urinary copper excretion, hair copper concentrations, and urinary thiobarbituric acid-reactive substances were significantly higher during the second MRU period than during the first. Polymorphonuclear cell count, the percentage of white blood cells, lymphocyte count, and interleukin 2R were affected by copper supplementation. Antibody titer for the Beijing strain of influenza virus was significantly lower in supplemented subjects after immunization than in unsupplemented control subjects. CONCLUSIONS: Under highly controlled conditions, long-term high copper intake results in increases in some indexes of copper status, alters an index of oxidant stress, and affects several indexes of immune function. The physiologic implications of these changes are unknown.

Adult↗
PubMed2003

The role of juvenile hormone in immune function and pheromone production trade-offs: a test of the immunocompetence handicap principle.

The immunocompetence handicap hypothesis postulates that secondary sexual traits are honest signals of mate quality because the hormones (e.g. testosterone) needed to develop secondary sexual traits have immunosuppressive effects. The best support for predictions arising from the immunocompetence handicap hypothesis so far comes from studies of insects, although they lack male-specific hormones such as testosterone. In our previous studies, we found that female mealworm beetles prefer pheromones of immunocompetent males. Here, we tested how juvenile hormone (JH) affects male investment in secondary sexual characteristics and immune functions in the mealworm beetle, Tenebrio molitor. We injected male mealworm beetles with JH (type III) and found that injection increased the attractiveness of male pheromones but simultaneously suppressed immune functions (phenoloxidase activity and encapsulation). Our results suggest that JH, which is involved in the control of reproduction and morphogenesis, also plays a central role in the regulation of a trade-off between the immune system and sexual advertisement in insects. Thus, the results reflect a general mechanism by which the immunocompetence handicap hypothesis may work in insects.

Animals↗
PubMedDate not supplied

Effects of the malononitrilamide FK778 on immune functions in vitro in whole blood from non-human primates and healthy human volunteers.

BACKGROUND: FK778, a malononitrilamide analog of leflunomide, is currently being investigated for use in clinical transplantation. METHODS: Whole blood from cynomolgus monkeys (n=4) and healthy human volunteers (n=4) was incubated with different concentrations of FK778 and stimulated with mitogens in culture medium. Lymphocyte proliferation was assessed by tritium-labeled thymidine incorporation and by flow-cytometric analysis of expression of proliferating cell nuclear antigen on cells in S/G(2)M phase. Flow cytometry was also used to assess expression of T and B lymphocyte activation surface antigens and production of intracellular cytokines by T cells. RESULTS: Not only lymphocyte proliferation, but also expression of various T cell surface antigens (CD25, CD11a, CD95, CD154) was suppressed by FK778. Fifty percent effective concentration values for the different immune functions were lower in human blood than in blood from cynomolgus monkeys. CONCLUSIONS: FK778 inhibits multiple immune functions. Their flow cytometric evaluation can be used to assess the effects of the drug in vivo.

Alkynes↗
PubMed2002

Effects of arginine, L-alanyl-L-glutamine or taurine on neutrophil (PMN) free amino acid profiles and immune functions in vitro.

The objective of this study was to determine the effects of arginine, L-alanyl-L-glutamine (Ala-Gln) or taurine on polymorphonuclear leucocyte (PMN) free amino acid profiles, superoxide anion (O2-) generation, hydrogen peroxide (H2O2) formation and released myeloperoxidase activity (MPO). Arginine led to significant increases in PMN arginine, ornithine, citrulline, aspartate, glutamate and alanine concentrations as well as increased H2O2-generation and MPO activity while O(2-)-formation was decreased. Ala-Gln caused significant increases in PMN free glutamine, alanine, asparagine, aspartate, glutamate, ornithine, arginine, serine and glycine concentrations and increased PMN immune functions. Taurine significantly increased PMN free taurine profiles, reduced PMN neutral amino acid content and decreased H2O2- and O(2-)-formation while MPO was increased. Altogether, the pharmacological regimens which enhance the supply of arginine, Ala-Gln or taurine in whole blood significantly affect PMN "susceptible free amino acid pool". This may be one of the determinants in PMN nutrition considerably influencing PMN immune functions. Introduction Polymorphonuclear leucocytes (PMN) ensure an important part of non-specific cell-mediated immunity and play a crucial role in the host defense

Adult↗
PubMed1994

[Effects of crowding on immune functions in mice].

The effects of several types of crowding on immune functions were studied in mice. This study consisted of two experiments. Experiment one: Male BALB/c mice were initially housed in groups of four mice per cage. After fourteen days of acclimation, the mice were randomly divided into three groups, Control (four mice per cage, control group), Crowd-I (four mice per small space) and Crowd-II (sixteen mice per cage). These conditions were maintained for seven days. The results of experiment one were as follows: (1) The percentage of lymphocytes in the blood of Crowd-II was significantly lower than that of Control (p < 0.05). (2) The percentage of neutrophils and the absolute number of neutrophils in blood of Crowd-II were significantly higher than in Control (p < 0.05). (3) Superoxide production activity (NBT reduction activity) of blood neutrophils in Crowd-II tended to be depressed, and phagocytic activity of neutrophils was significantly depressed in Crowd-II as compared with Control (p < 0.01). These results suggest that the complexity of interrelationships among mice caused by an increase in the number of animals per cage is a very important stress factor. Experiment two: Male BALB/c mice were initially housed in groups of five mice per cage. After fourteen days of acclimation, the mice were divided into three groups, Control (five mice per cage, control group), Crowd-(1) (five mice per cmall space) and Crowd-(2) (twenty mice per cage). In Control and Crowd-(1), the same mice were used as in the acclimation period. These conditions were maintained for seven days. In this period, on the second day, all the mice were injected intraperitoneally with sheep red blood cells (SRBC). The results of experiment two were as follows: (1) The specific humoral immune response to SRBC was investigated in terms of the number of PFC in the spleens and hemagglutination in sera, but significant differences were not found among the groups. (2) Plasma IgG levels in the Crowd-(1) were significantly higher than those in Control (p < 0.05). (3) Both superoxide production activity and phagocytic activity of neutrophils were significantly depressed in Crowd-(2) as compared with Control (p < 0.01, respectively), whereas each neutrophil function of Crowd-(1) tended to be enhanced as compared with Control.

Animals↗
PubMed2005

[The prognostic value of cellular immunity function in patients with hepatocellular carcinoma].

OBJECTIVES: To study the changes of cellular immunity function in patients with hepatocellular carcinoma (HCC) and its correlation with disease severity. METHODS: T lymphocyte subsets and CD28 co-stimulation molecule in CD8+ T cells in 22 HCC patients were detected using three-color flow cytometry. Serum interleukin-2 (IL-2), transforming growth factor beta 1 (TGFbeta1), and interleukin-6 (IL-6) were determined by ELISA and radioimmunoassay. A group of 30 patients with chronic hepatitis B (CHB), liver cirrhosis (LC), or normal adults (NC) served as controls. RESULTS: Compared with NC, the number of CD8+CD28- T cells increased and CD8+CD28+ T cells decreased in patients with HCC. The number of CD4+ T cells, CD4+/CD8+ ratios, IL-2 level all decreased and CD8+ T cells, IL-6, TGFbeta1 levels all increased in patients with HCC, LC and CHB. The CD4+ T cells, CD4+/CD8+ ratios and IL-2 level in patients with HCC were lower than those with CHB. Serum IL-6 and TGFbeta1 in patients with HCC were higher than those with LC and CHB. The levels of IL-6 and TGFbeta1 correlated with the stages of the tumors. CONCLUSIONS: HCC patients have a cellular immunity dysfunction. Rectifying the imbalanced function could be a potential way for treating HCC. Measurement of these factors would be useful for early diagnosis and evaluating the prognoses of these patients.

Adult↗
PubMed1977

Immune function in ankylosing spondylitis: apparent relationship between streptococcal responses and HLA B27.

Immune function has been evaluated in 54 patients with ankylosing spondylitis (AS) and 26 controls. Cell-mediated immunity was assessed by skin testing with ubiquitous antigens, and humoral immunity by antibody responses to tetanus toxoid and Salmonella typhi vaccinations, and resting titres of anti-Streptolysin O, anti-E Coli, and isohemagglutinins. The AS patients had reduced delayed hypersensitivity responses to Candida, augmented responses to Streptococcal antigen and relatively low ASO titres. There was no generalized depression of humoral immunity, as indicated by the normal tetanus and Salmonella O responses and hyper-response to Salmonella H antigen. The E. Coli and isohemagglutinin titres were normal. These results indicate that patients with AS present a complex immunological profile, including exaggerated responses to some antigens and impaired responses to others. In view of the very high incidence of HLA-B27 in AS, it is possible that these findings are related to the effects of HLA associated immune response genes.

Adult↗
PubMed2001

Postgrafting administration of granulocyte colony-stimulating factor impairs functional immune recovery in recipients of human leukocyte antigen haplotype-mismatched hematopoietic transplants.

In human leukocyte antigen haplotype-mismatched transplantation, extensive T-cell depletion prevents graft-versus-host disease (GVHD) but delays immune recovery. Granulocyte colony-stimulating factor (G-CSF) is given to donors to mobilize stem cells and to recipients to ensure engraftment. Studies have shown that G-CSF promotes T-helper (Th)-2 immune deviation which, unlike Th1 responses, does not protect against intracellular pathogens and fungi. The effect of administration of G-CSF to recipients of mismatched hematopoietic transplants with respect to transplantation outcome and functional immune recovery was investigated. In 43 patients with acute leukemia who received G-CSF after transplantation, the engraftment rate was 95%. However, the patients had a long-lasting type 2 immune reactivity, ie, Th2-inducing dendritic cells not producing interleukin 12 (IL-12) and high frequencies of IL-4- and IL-10-producing CD4(+) cells not expressing the IL-12 receptor beta(2) chain. Similar immune reactivity patterns were observed on exposure of donor cells to G-CSF. Elimination of postgrafting administration of G-CSF in a subsequent series of 36 patients with acute leukemia, while not adversely affecting engraftment rate (93%), resulted in the anticipated appearance of IL-12-producing dendritic cells (1-3 months after transplantation versus > 12 months in transplant recipients given G-CSF), of CD4(+) cells of a mixed Th0/Th1 phenotype, and of antifungal T-cell reactivity in vitro. Moreover, CD4(+) cell counts increased in significantly less time. Finally, elimination of G-CSF-mediated immune suppression did not significantly increase the incidence of GVHD (< 15%). Thus, this study found that administration of G-CSF to recipients of T-cell-depleted hematopoietic transplants was associated with abnormal antigen-presenting cell functions and T-cell reactivity. Elimination of postgrafting administration of G-CSF prevented immune dysregulation and accelerated functional immune recovery.

Acute Disease↗