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PubMed1975

Properties and activities of transfer factor.

Although there is agreement that transfer factor endows skin test-negative subjects with the ability to develop the delayed allergic responses of the transfer factor donors, there is little direct information on the mechanism of this phenomenon or on the nature of the active components (s). This report reviews some of the known effects of transfer factor or immune responses and inflammation. It is concluded that transfer factor has multiple sites of action, including effects on the thymus, on lymphocyte-monocyte and/or lymphocyte-lymphocyte interactions, as well as direct effects on cells in inflammatory sites. It is also suggested that the "specificity" of transfer factor is determined by the immunologic status of the recipient rather than by informational molecules in the dialysates. Finally, it is proposed that many effects of transfer factor may be due to changes in intracellular cyclic nucleotide content, especially accumulation of cGMP, in immunologically reactive cells.

Antibody Formation↗
PubMed1979

[Technics and applications of transfer factor (author's transl)].

Transfer factor is produced by dialysis of repeatedly frozen and thawed pooled buffy coats of healthy blood donors. However, "specific Transfer Factor" of bacteriological or mycological type, prepared from hyperimmunized donors would be more effective for restoring cellular immunity.

Hematologic Diseases↗
PubMed1975

Lymphocyte transformation, IgE and T-cells in eczema vaccinatum treated with transfer factor. A case report.

Transfer factor (TF) was given to intensify the cell-mediated immune reactions in an atopic patient with generalized vaccinia. The patient showed marked reactivity of peripheral blood lymphocytes to stimulation with phytohaemagglutinin and pokeweed mitogen, but also in nonstimulated cultures. However, later tests with mitogen stimulation of lymphocytes indicated a defective cellular defence mechanism. The addition of autologous plasma to lymphocyte cultures depressed the reactivity of PHA-stimulation considerably. Initially, the patient also showed a normal T-lymphocyte count in peripheral blood, but six months after her vaccinia, extremely high serum IgE levels and a decreased percentage of T-lymphocytes was observed. Although an evaluation of the clinical effect of transfer factor injection is difficult, it should be noted that the patient's temperature immediately fell to normal, and her general health improved following treatment.

Adolescent↗
PubMed1979

Transfer factor in immunodeficiency diseases.

Results of therapeutic trials of transfer factor in a number of laboratories suggest clinical benefit and enhancement of immunological reactivity in patients with primary or secondary immunodeficiency diseases. Long term follow-up of 32 patients with the Wiskott-Aldrich syndrome suggested that transfer factor caused conversion of immunologic reactivity, apparent clinical benefit, and prolonged survival in some, but not in all patients. In 18 patients with disseminated (Stage III) malignant melanoma treated with surgery and transfer factor, survival was better than would ordinarily be expected for disseminated disease (78% with mean follow-up of 2 years). A randomized trial has been initiated which will answer the question of the efficacy of transfer factor as surgical adjuvant therapy in malignant melanoma. Studies in human subjects suggested that transfer factor does not cause enhancement of reactivity in normal subjects, when evaluated in a controlled, double-blind fashion. Similar controlled studies in immunodeficient patients are necessary to ascertain whether transfer factor does cause enhancement of immune responses in these patients. Based on these observations, a guinea pig model was developed in which transfer factor caused abrogation of tolerance to ABA-Tyrosine.

Child↗
PubMed1976

Transfer factor therapy in patients with cancer.

The objective of this study was to utilize transfer factor to stimulate cell-mediated immunity to specific tumor antigens in cancer patients. Thirty-five selected patients with advanced recurrent cancer, who were not suitable for further conventional therapy, were treated with transfer factor. Transfer factor was prepared from cohabitants of the patients and administered at 2-week intervals. This immunotherapeutic approach produced a clinical effect in 13 patients in terms of regression of tumor (1), arrest of metastatic disease (14), or pain relief (14). Conversion of dermal reactivity to specific tumor antigens was observed during periods of clinical improvement. Despite continued immunotherapy, the duration of clinical improvement was short (2 weeks to 12 months). Seven of the 11 patients not responding to therapy exhibited serum blocking of lymphocyte responsiveness. In 11 patients there is insufficient data to evaluate the clinical effectiveness of this therapy. The results suggest that transfer factor can stimulate specific cell-mediated immunity in cancer patients and produce a clinical effect on tumor under certain circumstances.

Antigens, Neoplasm↗
PubMed1977

Long-term transfer factor treatment in severe atopic dermatitis.

Transfer factor therapy was applied in three patients with severe atopic dermatitis and given at regular intervals for 1 1/2 years. Clinically, slight improvements were seen, attacks of impetigo ceased and admissions to hospital were not necessary. However, IgE concentrations in serum remained constantly high in all cases and the absolute number of T and B lymphocytes was continuously subnormal despite treatment. The in vitro cellular reactivity to PPD as assayed by a leucocyte migration test was not significantly altered in the patients, although a slight increase was found early on in the therapy. Finally, a serum factor inhibiting leucocyte migration and appearing simultaneously with attacks of impetigo disappeared during treatment. In conclusion, no convincing effect of transfer factor therapy was encountered in immune parameters and no major alterations were found in the status of the patients' atopic dermatitis.

Adult↗
PubMed1975

Restoration of cell-mediated immune responses with transfer factor.

Five anergic patients with chronic mucocutaneous candidiasis were given transfer factor from donors with positive delayed reactions to Candida. In each recipient, the delayed skin reactions of the transfer factor donors appeared in the recipients and no recipient developed reactivities not possessed by the donor. Prior to injection of transfer factor, in vitro stimulation of the patients' lymphocytes with antigens did not result in MIF production, however, after transfer factor this response was positive. Therapy with transfer factor alone did not have therapeutic benefit, however, in 2 patients treatment with amphotericin-B followed by transfer factor has produced cutaneous remissions of 18 months.

Candida albicans↗
PubMed1975

Randomized trial of transfer factor treatment of human warts.

Dialysed transfer factor, prepared from the leucocytes of a donor whose warts had undergone recent spontaneous regression, was used in the treatment of a child with the Wiskott--Aldrich syndrome. The child then had a spontaneous regression at multiple warty areas. A similar relationship was seen in four otherwise healthy patients in a pilot study. A randomized double-blind study of thirty patients failed to confirm a causal relationship between the transfer factor therapy (equivalent to 2-1 X 10(8) leucocytes) and wart regressions. The need for randomized trials of transfer factor therapy for diseases with a variable natural history is emphasized.

Adolescent↗
PubMed1975

Transfer factor therapy in patients with subacute sclerosing panencephalitis.

Thirteen patients with subacute sclerosing panencephalitis (S.S.P.E.) at different stages of the disease were admitted for transfer factor treatment. The transfer factor was prepared from non-selected blood bank donors. The activity of the transfer factor was tested in patients with diseases other than S.S.P.E. and was found to be either clinically or immunologically active. Regardless of the number of transfer factor units applied a significant influence on the course of the disease was not apparant. The observed intermittant improvement of 3 patients was considered as spontaneous remission which is known to occur occasionally in S.S.P.E. The humoral and cellular immune response before and after transfer factor therapy did not reveal significant changes which could be correlated with transfer factor therapy.

Adolescent↗
PubMed1975

Improvement in delayed hypersensitivity in Hodgkin's disease with transfer factor: lymphapheresis and cellular immune reactions or normal donors.

Passive transfer of delayed hypersensitivity was achieved, with normal transfer factor, in patients with Hodgkin's disease in remission. The cellular immune responses of the recipients improved. It is suggested that, in addition to specific effect the transfer factor (or factors) has a nonspecific effect causing improvement in the state of delayed hypersensitivity of the recipient in general. The average number of E-rosette T lymphocytes was 46.3% after the transfer factor treatment in Hodgkin's disease. The control patients with Hodgkin's disease, not receiving transfer factor, had a value of 37.8%. Removal of 4.9 X 10(9) to 1.08 X 10(10) lymphocytes did not diminish the delayed hypersensitivity of the donor. Side effects attributable to transfer factor were not seen.

Cell Count↗
PubMed1976

Transfer-factor therapy in multiple sclerosis.

The effect of transfer factor prepared from relatives of patients with multiple sclerosis (M.S.) and from unrelated donors on the clinical course of M.S. has been studied in fifteen male and fifteen female patients. Some patients were given transfer factor and some placebo (physiological saline). Results of three independent clinical examinations by different neurologists and subjective assessments by the patients showed no difference between those given transfer factor and those given placebo.

Adolescent↗
PubMed1976

Therapy with parent's lymphocyte transfer factor in children with infection and malnutrition.

Transfer factor (T.F.) prepared from 5 x 10(8) lymphoid cells from 500 ml of a parent's blood was given to 40 Australian aboriginal children aged 2-46 months who had been in hospital with acute infection. Many had protein-calorie malnutrition. These and a control group of 35 similar children were assessed blind for at least 12 months. In T.F.-treated children there were significantly fewer episodes of diarrhoeal disease for periods in excess of 26 weeks. Recurrent moderate diarrhoeal disease was particularly reduced, and the onset of severe gastroenteritis may have been delayed. There was no protection against chest, middle-ear, or skin infection.

Adult↗
PubMed1979

A placebo controlled clinical trial of transfer factor in lepromatous leprosy.

The effects of repeated injections of transfer factor over a period of 20 weeks were investigated in fourteen bacteriologically positive patients at the lepromatous side of the leprosy spectrum. All patients showed negative (0 mm induration) skin tests to M. leprae antigens (i.e. leprolin and lepromin). Of these patients, seven were treated with transfer factor with a total of 9 units (1 unit being equivalent to 5 x 10(8) lymphocytes) and seven with a placebo. Maintenance treatment with clofazimine was continued. Transfer factor was prepared from the lymphocytes of donors who showed positive skin tests to M. leprae antigens (i.e. leprolin greater than or equal to 12 mm induration, average 15.5 mm or lepromin greater than or equal to 8 mm induration, average 13.6 mm), as well as a positive lymphocyte transformation in vitro to M. leprae (the average transformation being higher than the average transformation of lymphocytes of tuberculoid leprosy patients). No differences were found between the two groups as regards the clinical course of the disease, the histopathological and bacteriological evaluation of skin biopsies, changes in skin test reactivity to various antigens (i.e. lepromin, leprolin, PPD, Mumps, C. albicans, Tr. rubrum and Varidase), as well as the lymphocyte transformation in vitro to various mitogens (i.e. PHA, PWM, Con A) and antigens (i.e. M. leprae, leprolin, PPD, BCG, Mumps, C. albicans, Trichophyton and Varidase). No evidence was found to suggest that transfer factor is a valuable adjuvant in the treatment of lepromatous leprosy patients or that it increases cell-mediated immune reactivity towards M. leprae.

Antigens, Bacterial↗
PubMed1975

Stimulation of monocyte cGMP by leukocyte dialysates. An antigen-independent property of dialyzable transfer factor.

We studied the effects of dialysates from leukocyte lysates containing dialyzable transfer factor activity and other leukocyte dialysates devoid of transfer factor activity on accumulation of cyclic nucleotides in human leukocytes. Dialysates from normal leukocytes produced 4- to 11-fold increases in leukocyte cGMP, and experiments with purified cell populations revealed that the increases were predominantly, if not entirely, in blood monocytes. Substances that increased monocyte cGMP could be obtained from several cell populations including mononuclear cells from Hypaque-Ficoll gradients, plastic-adherent monocytes, nonadherent lymphocytes, and neutrophils, but were not present in dialysates of leukemic lymphocytes from patients with the Sezary syndrome. Moreover, dialysates that increased leukocyte cGMP had essentially no effect on intracellular cAMP. Dialysates of lysed mononuclear cells contained serotonin, ascorbate, and an unidentified cholinergic activity, agents known to increase leukocyte cGMP. After passage of dialyzable transfer factor from mononuclear cells through a gel-filtration column, four fractions were obtained that increased leukocyte cGMP. Two of these fractions contained ascorbate; two other active fractions, including one that also caused conversion of delayed skin tests, did not contain detectable ascorbate or serotonin. The dialysate of lysed neutrophils also increased cGMP, but this activity was limited to the column fractions which contained ascorbic acid. These observations raise the possibility that alterations in monocyte cGMP content could modulate either the specific antigen-dependent, or, more likely, the antigen-independent activities in preparations of transfer factor.

Ascorbic Acid↗
PubMed1977

Disseminated varicella infection: treatment with transfer factor in a patient with Hodgkin's disease.

Treatment with transfer factor in a patient with disseminated varicella infection complicating stage IV Hodgkin's disease is described. The patient, a 24-year-old woman, showed transient clinical improvement and restoration of immune response to varicella-zoster antigen after receiving transfer factor. Though she later died from septicaemia, further trials of treatment of disseminated viral infection in patients with Hodgkin's disease with transfer factor are indicated.

Adult↗