Administration Of Transfer Factor Research Articles

Transfer factor treatment in management of peritonitis condition: An experimental study in rat

BackgroundThere is a role for the immune system in improving the outcome of peritonitis cases in children. Transfer factors are one immunomodulatory treatment that can increase the activity of natural killer (NK) cells to produce interferon-gamma (IFN-γ), which is thought to increase the phagocytic activity of macrophages. This study analyzed the effects of transfer factors on the phagocytic activity of macrophages in the intraperitoneal fluid of a Wistar rat model of peritonitis. MethodsThis experimental study had a post-test-only control group design and was carried out at the Laboratory of Pharmacology and Microbiology of Padjadjaran University, Bandung, Indonesia. It analyzed the effect of transfer factors on the phagocytic activity of macrophages in the intraperitoneal fluid of Wistar rats experiencing peritonitis after being injected with Escherichia coli. An unpaired comparative t-test was performed using the SPSS program to analyze the difference between transfer factor administration and macrophage phagocytic activity levels. ResultsThere was a statistically significant difference between the phagocytosis index values of macrophages in samples treated with transfer factors and those that were untreated (p = 0.005). ConclusionsTransfer factors increased the phagocytic activity of macrophages in a Wistar rat model of peritonitis. This suggests that transfer factors could have a role as an immunomodulatory treatment for peritonitis.

Comparison of bovine transfer factor and Micotil®: effects on health and performance of receiving heifers (2004)

Transfer factors are antigen-specific products of T lymphocytes that are capable of transferring delayed-type hypersensitivity and cell-mediated immunity. We evaluated bovine transfer factor (TF) for use in receiving cattle. Crossbred beef heifers (n = 665) initially weighing 495 lb were used to determine the effects of TF on the health and performance of beef cattle during a 36-day receiving period. Heifers were processed within 24 hours after arrival. Treatments were subcutaneous injection with 1.5 ml of Micotil/100 lb of body weight or oral administration of 700 mg of TF isolated from bovine colostrum. Heifers given TF during initial processing received an additional 700 mg/day of TF in the diet on days 2 through 5. The percentage of heifers treated at least one, two, or three times for bovine respiratory disease (BRD) was greater (P<0.01) for heifers given TF than for heifers given Micotil (72.5 vs. 47.1; 31.5 vs. 14.7; and 18.0 vs. 4.2, respectively). There were no differences between TF and Micotil with respect to dry matter intake, weight gain, or gain efficiency of heifers. Subsequent in vitro fermentations indicated that TF protein is readily degraded by ruminal microbes. Oral administration of TF was not as effective as Micotil injection in decreasing BRD in receiving cattle.

Adjuvant treatment using transfer factor for bronchogenic carcinoma: Long-term follow-up

Transfer factor, a dialyzable lymphocyte extract that may act as an immune stimulator by transferring antigenspecific immunity between genetically dissimilar individuals, was administered in a prospective, randomized study to patients with non-small cell bronchogenic carcinoma. Between 1976 and 1982, 63 patients who underwent pulmonary resection, mediastinal lymph node dissection, and, when indicated by the presence of mediastinal lymph node involvement, mediastinal irradiation were randomized into two groups. Group 1 (n = 28) received 1 mL of pooled transfer factor at 3-month intervals after operation; group 2 (n = 35) served as controls and received saline solution. There were no statistically significant differences between the two groups with respect to age, sex, tumor histology, stage of disease, or extent of resection. One patient was lost to follow-up at 96 months; follow-up was complete in all others through July 1990. In patients receiving transfer factor, the 2-, 5-, and 10-year survival rates were 82%, 64%, and 43% respectively, whereas in controls they were 63%, 43%, and 23%. Survival in patients receiving transfer factor was consistently better than in those receiving placebo. Furthermore, survival in patients receiving transfer factor was greater at all stages of disease for both adenocarcinoma and squamous cell carcinoma. Although these long-term results were not statistically significant using survival analysis with covariates ( p = 0.08), they confirm our previously reported short-term findings suggesting that administration of transfer factor, either through nonspecific immune stimulation, enhancement of cell-mediated immunity, or an as yet undefined mechanism, can improve survival in patients with bronchogenic carcinoma.

Treatment of cryptosporidiosis with oral bovine transfer factor

Cryptosporidia are intestinal protozoans long known to cause diarrhea in humans, especially those with acquired immune deficiency syndrome (AIDS). When transfer factor prepared from calves which possessed delayed-type hypersensitivity to Eimeria bovis was given to nonimmune calves and mice it conferred protection against clinical infection (coccidiosis). Recent studies with oral bovine transfer factor have shown that it can confer cell-mediated immunity to humans. Based on these findings we decided to treat eight AIDS patients suffering from Cryptosporidium-associated diarrhea with transfer factor prepared from calves immune to Cryptosporidium- Prior to treatment with transfer factor, three patients had been treated with spiramycin, one patient with α-difluoromethylornithine (DFMO), and one patient with furazolidone for greater than 1 month without clinical or laboratory improvement. Following administration of transfer factor, five or eight patients exhibited a decrease in the number of bowel movements and the development of formed stools. Cryptosporidium was eradicated from the stools of four patients but two of these patients subsequently relapsed and one patient continued to have diarrhea despite the absence of Cryptosporidium in the stool. One patient has been free of diarrhea and Cryptosporidium for 2 years after discontinuation of transfer factor therapy.

Outbreak of respiratory syncytial virus in France.

A report is given of an outbreak of respiratory syncytial virus infection in a neonatal unit in France. Twenty-three of 32 infants were infected (72%) despite infection control procedures. Prophylactic administration of non-specific gamma globulins was associated with a significant decrease in infection rate (p less than 0.05). The administration of transfer factor to infected infants was also associated with a significantly lower rate of severe respiratory diseases (p less than 0.05).

Investigations of transfer factor activity in resistance to Trichostrongylus colubriformis infections in guinea-pigs.

Resistance to challenge infection with Trichostrongylus colubriformis was studied in an outbred strain of guinea-pigs. Resistance was conferred by previous infections of 50 or 100 infective larvae and by intraperitoneal, intramuscular and subcutaneous administration of dialysed transfer factor prepared from guniea-pigs infected with T. colubriformis, by intraperitoneal administration of transfer factor prepared from the blood of sheep infected with T. colubriformis and on one of three occasions using transfer factor prepared from guinea-pigs which had not been infected with T. colubriformis. No significant resistance was transferred by administration of antigen prepared from adult T. colubriformis, or by non-dialysed transfer factor, or by dialysed transfer factor prepared from T. colubriformis-infected guinea-pig tissue which had been stored for several months at - 20 degrees C.

Nephropathy in the Wiskott-Aldrich Syndrome

Nephropathy was detected in five of 32 patients with the Wiskott-Aldrich syndrome who were participating in a study of transfer factor (TF) therapy. In two patients, nephropathy was present before TF and did not appear changed by TF therapy. One of these patients subsequently developed progressive renal failure requiring dialysis beginning 5 1/2 years after TF therapy. In two patients, decreased renal function appeared very soon after the administration of TF. One patient showed gradually decreasing renal function beginning after two years of TF therapy. An additional patient was identified who died with renal failure without having received TF. The results suggest that renal failure occurs in the Wiskott-Aldrich syndrome more frequently than generally recognized and that administration of TF may precipitate or accelerate the renal disease in patients with this syndrome.

The in vivo antibody responses to polymerized flagellin (POL) in man

The capacity of antibody response in man was evaluated by a single intradermal injection of polymerized flagellin (POL) from Salmonella adelaide. The antibody was titrated in sera (with or without treatment with 2-mercaptoethanol) by microhemaglutination using antigen-sensitized group O red blood cells (RBC). The naturally occurring antibody to POL was detected in 64% of 190 nonimmunized healthy subjects. Its frequency and titer gradually increased with age. In 10 healthy adult subjects and 15 patients with miscellaneous diseases, a good response with both IgM and IgG antibody was induced. The IgM to IgG switch-over was more clearly elucidated in subjects without the natural antibody. In 12 immunodeficient patients, the subjects with T- and/or B-cell dysfunction did not produce or poorly produced the antibody. Four subjects with Wiscott-Aldrich syndrome (WAS) revealed a comparatively high antibody response; two of them became significantly responsive to POL after administration of transfer factor and reimmunization with POL. POL is one of the best applicable test antigens and appears to act as a T-independent immunogen in man.

Transfer factor and cellular reactivity to varicella-zoster antigen in childhood leukemia

The present studies were designed to evaluate possible efficacy of specific human transfer factor (TF) in preventing or attenuating varicella-zoster (VZ) infection in children with acute lymphocytic leukemia (ALL). TF was prepared following leukapheresis of adult donors who were convalescing from chicken pox. Recipients were VZ seronegative children with ALL, 12 in remission and 3 in relapse; a single injection of TF was given equivalent to 10 8 lymphocytes per 7 kg body wt. The following VZ-specific parameters were measured: lymphocyte blastogenesis, cytotoxicity and leukocyte inhibitory factor (LIF) production, and indirect fluorescent and CF antibody titers. No patients in relapse converted immune response while 10 12 in remission developed positive reactivity in at least one assay of cell-mediated immunity (CMI); 3 12 were positive in all three parameters of CMI and 8 12 in two assays. Cytotoxicity was the most consistently positive test following TF administration. No patients developed VZ antibody. Seventeen months follow-up has demonstrated persistent cellular immunity.

Transfer factor from BCG-sensitized mice.

A mouse model was established for the study of transfer factor (TF). TF was extracted from the spleens of sensitized mice and examined for activity by the footpad test, which showed that mouse and human TF possessed similar properties. Parenteral administration of TF imparted to unsensitized mice immunologically specific, delayed type hypersensitivity within 24 hr. The magnitude of the response the recipients was proportional to the dose of TF. TF activity was relatively heat-stable, detectable in a fraction of molecular weight of ca 1,000 and apparently contained nucleic acids. Nude mice responded negatively to TF but following administration of viable naive spleen cells a positive response was observed, which suggests that the thymus plays an important role in the expression of TF phenomenon and that the target of TF is the T cells.

Transfer factor is ineffective in amyotrophic lateral sclerosis

Sixty-six patients with amyotrophic lateral sclerosis (ALS) participated in a double-blind, placebo-controlled study of transfer factor. A structured rating score of neurological function was recorded after each monthly administration of transfer factor or placebo. Statistical analysis of mean scores for all patients and for those with specific clinical abnormalities showed no significant difference between the two groups. There was no evidence of therapeutic value for transfer factor. During the observation period of nearly one year, more than two-thirds of the deterioration occurred in the first six months. Meaningful clinical trials of other potential therapeutic agents could probably be conducted within six months in double-blind crossover trials.

Chronic Mucocutaneous Candidiasis and Transfer Factor

Chronic mucocutaneous candidiasis (CMCC) is a syndrome characterized by persistent or recurrent Candida infection involving mucous membranes, contiguous and distant skin areas, and nails; it is often associated with an endocrinopathy (endocrine-candidiasis syndrome). There are several forms of this syndrome. Whether these clinical variants and the presence or absence of endocrinopathy represent different forms of a single disease or separate entities is not yet known. Several immunologic defects have been described, but no consistent abnormality has been noted. The author has proposed the hypothesis “immune deviation theory” in the pathogenesis of CMCC.The efficacy of restoration of cellular immunity in therapy of patients with certain chronic infectious or neoplastic diseases is under evaluation in several centers. Theoretically, a substance such as transfer factor (TF) is an ideal candidate for this therapy. TF, a dialyzable substance from blood leukocytes, selectively endows recipients with the cellular immune responses of the leukocyte donors. Moreover, it does not contain intact leukocytes and therefore does not sensitize the recipient to HL-A antigens and cannot induce graft-versus-host disease.Twelve patients with CMCC were treated with TF from randomly selected donors in conjugation with administration of certain antifungal agents such as clotrimazole or amphotericin-B. Mucocutaneous symptoms and signs were predominant at the time that the TF injections were started. Six patients showed remarkable improvement both immunologically and clinically. Patients with CMCC in association with endocrinopathy are unlikely to respond clinically to TF administration although in vitro and/or in vivo changes in cell-mediated immunity may be observed. These results indicate that TF therapy may be beneficial in some cases with CMCC.

Deficient neutrophil function in a patient with chronic mucocutaneous candidiasis, thymoma and myasthenia gravis

The case of a 68-year-old man who suffered the onset of chronic mucocutaneous candidiasis, thymoma, myasthenia gravis and a reversible neutrophil dysfunction during adult life is reported. All tests for humoral and cellular immunity proved normal. Thymectomy and the administration of transfer factor had no effect on the skin disease. Long-term oral administration of 5-fluorocytosine almost cleared the skin lesions; the neutrophil defect disappeared.

TRANSFER FACTOR IN CHRONIC AND RECURRENT RESPIRATORY TRACT INFECTIONS IN CHILDREN

Five cases with abnormal sensitivity to respiratory tract infections are described. The cases showed a marked impairment in their cell mediated immunity state. Administration of a chromatographically purified transfer factor component increased the skin test sensitivity to common recall antigens. Interestingly, a similar effect in skin reactivity was observed with repeated skin tests alone, when antigen concentrations, initially high enough to cause a positive reaction, were used. Neither the administration of transfer factor nor skin testing with high antigen concentrations had an effect on blast transformation percentages. The therapy with chromatographically purified transfer factor appeared promising on the clinical condition of the patients.

A Special Report: Four-year Study of a Boy with Combined Immune Deficiency Maintained in Strict Reverse Isolation from Birth

A 4-year study of a boy with combined immune deficiency is presented, and the impact of this disease on various aspects of his growth and development is examined. There is no evidence of immune deficiency in either parent or in the genetic background on the maternal side. Three children of a brother of the mother's father may have had immune deficiencies but two have grown to be teenagers with no problems. Another died. At autopsy, however, lymph nodes appeared normal. The deceased older brother had severe combined immune deficiency (SCID). The autopsy findings showed Pneumocystis carinii pneumonia to be the direct cause of death and these findings contributed to the diagnosis of SCID. After a successful germ-free birth, the male infant (DV) was placed in the isolator. Laboratory tests were normal except that the x-rays showed no thymic shadow, his absolute lymphocyte count ranged from 399-440/mm and the lymphocytes showed no proliferative response to phytohemagglutinin (PHA). Specific tests showed the antibody-producing immune system and the cell-mediated immune system to be severely defective. The patient's lymphocytes elicited positive responses by lymphocytes from father, mother, and sister. Subsequent search in national and international tissue-typing laboratories has shown four HLA matches but none has been nonreactive in mixed lymphocyte culture (MLC). therefore, this patient has remained in isolation to the present; now he is 4 years old. Approximately 35 species of microorganisms, mostly transient contaminants, have been isolated, taking into account that the same organism may have been identified under different names in different laboratories. Those isolated frequently and in sufficiently high concentration to indicate colonization have been speciated as follows: anaerobes-Propionibacterium acnes, Lactobacillus catenaforme (disappeared spontaneously), Bacteroides oralis ss. elongatus, Clostridium (perenne, hastiforme, bifermentans), Bacteroides clostridiiformis ss. clostridiiformis; aerobes-Alcaligenes faecalis (eradicated by antibiotics), Staphylococcus epidermidis, Enterobacter agglomerans, Microcossu sp. subgroup 1, Bacillus pulvifaciens (disappeared spontaneously); yeasts-Candida (tropicalis, parapsilosis). Seven are considered to be probable components of the current autoflora: P. acnes, C. bifermentans, B. clostridiiformis ss. clostridiiformis, S. epidermidis, Micrococcus sp. subgroup 1, E. agglomerans, C. parapsilosis. No viruses or protozoa have been isolated. At age 3 years, the mean quantitation of anaerobic cells was 7.9 X 10(7) viable cells/g feces; this falls short of the mean anaerobic load from normal children. The mean aerobic concentration was 1.2 X 10(8) viable cells/g feces, not unlike normal children. Qualitatively his flora has abnormally few species and lacks those most common in normal subjects. This child has had no evidence of infection and has always been in excellent health even though some organisms which could be pathogenic under some circumstances have been isolated...

In vivo and in vitro evaluation of cell-mediated immunity in patients with paracoccidioidomycosis

The cellular immune response to specific and nonspecific agents was investigated. both in vivo and in vitro, in 19 patients with paracoceidioidomycosis. In addition, the immunologic study of an investigator aceidentally inoculated with P. brasiliensis was included in this study. Nearly half of the patients showed depressed cell-mediated immune responses, as evaluated by intradermal tests with an antigenic preparation from P. brasiliensis (P.b.Ag.), ubiquitous antigens, and by the ability to develop sensitization to 2,4-dinitrochlorobenzene. A similar proportion of impaired responses was observed when the patients' lymphocytes were cultured with phytohemagglutinin (PHA). C'. albicans antigen and P.h.Ag. A factor was detected in the plasma of some patients which reduced the ability of patients' and normal lymphocytes to undergo blastic transformation. A positive correlation was found between the ability to develop delayed cutaneous hypersensitivity reactions to P.b.Ag. and other ubiquitous antigens, normal in vitro responsiveness to PHA and the absence of humoral blastogenic inhibitory factor. The inhibition of leukocyte migration, but not lymphocyte transformation, correlated positively with delayed hypersensitivity. The percentage of T lymphocytes was significantly reduced in the group of patients, being the absolute number and percentage of B cells bearing receptors tor complement normal. Two polar immunological patterns emerged. One characterized by positiveness in the skin test to P.b.Ag. and lack of significant abnormalities in cellular immunity, and another anergic to P.b.Ag., with cell mediated immunity severely depressed. Between the two polar groups, there were patients with intermediary patterns of immune response. This paper also includes the results obtained with the administration of transfer factor and levamisole to some of the patients.

Selective severe cellular immunodeficiency: Effect of thymus transplantation and transfer factor administration

Two sisters from one family with a selective cellular immunodeficiency are described. The first girl born was admitted to the hospital at 10 months of age with generalized vaccinia following smallpox vaccination. Thymus-dependent immunity could not be demonstrated, whereas humoral immunity was present. She was treated with several thymus transplants and transfer factor injections, resulting in healing of the vaccinia lesions and partial, but transient, restoration of the thymus-dependent immunity. In spite of this success she developed a lymphosarcoma and died at the age of 3 years. Her younger sister was admitted at the age of 1.5 years and was suffering then from a fatal graft-versus-host reaction following a blood transfusion given elsewhere. Clinical and immunological findings of the two patients are presented in detail.

Immunologic and clinical improvement of progressive coccidioidomycosis following administration of transfer factor

Three patients with progressive coccidioidomycosis were given preparations of transfer factor (TF). Adverse reactions to TF were minimal. Following TF administration two of these patients had prolonged clinical remissions in their coccidioidal disease. Cellular immune responses were sequentially evaluated by coccidioidininduced delayed-type skin tests, lymphocyte blast transformation and macrophage inhibition factor production (MIF). These three patients each exhibited different cellular immune patterns before and after TF administration. Two patients converted their coccidioidin skin tests, and one converted lymphocyte transformation response to coccidioidin. Also, TF apparently favorably affected the MIF response in all three patients.

The Wiskott-Aldrich syndrome. Results of transfer factor therapy.

12 patients with Wiskott-Aldrich syndrome were treated with therapeutic doses of transfer factor in an attempt to induce cellular immunity. Clinical improvement was noted after transfer factor therapy in 7 of the 12 patients treated. Because this disease has a variable course and temporary spontaneous improvement can occur, the observed improvement cannot necessarily be attributed to the transfer factor. However, in two patients repeated remissions consistently followed transfer factor administration on repeated occasions. This included freedom from infections, regression of splenomegaly, and clearing of eczema. An unexpected finding was a decrease in bleeding in 3 of the 10 patients who had bleeding. Conversion of skin reactivity was obtained in all seven patients who clinically seemed to respond to transfer factor. In vitro studies performed after the administration of transfer factor demonstrated that the lymphocytes of the patients now produced migration inhibitory factor in response to appropriate test antigens, but did not undergo increased radioactive thymidine incorporation in response to the same antigens. A defect in the monocyte IgG receptors has been found in certain patients with the disease, and the current study shows that all patients with defective monocyte IgG receptors responded to transfer factor, whereas only one patient with normal receptors showed any response. This test may thus prove to be useful in predicting the results of transfer factor therapy in patients with Wiskott-Aldrich syndrome, although evaluation of a larger series of patients will be necessary to confirm this point. We conclude that cellular immunity can be induced, that there appears to be clinical benefit in certain patients with Wiskott-Aldrich syndrome by the use of transfer factor, and that this mode of therapy warrents trial in these patients and others with defects of cellular immunity.