Injections Of Transfer Factor Research Articles

Quality consistency evaluation of commercial transfer factor injections by chromatographic fingerprint combined with multivariate statistical analysis.

The current quality control methods relying mainly on chromogenic reaction can hardly ensure the quality and safety of the biochemical drug with complex chemical composition. Therefore, a chromatographic fingerprint method was developed for the quality evaluation of a multicomponent biochemical drug, transfer factor injection. High-performance liquid chromatography fingerprint was measured by using a C18 column (250 × 4.6mm, 5 µm) with a mobile phase composed of 0.1% trifluoroacetic acid-water and 0.085% trifluoroacetic acid-acetonitrile under gradient elution. The developed method was validated and was subsequently applied to 57 batches of commercial products which were sampled by National Drug Assessment Program. High-resolution mass spectrometry analysis was performed on characteristic peaks of fingerprints, and a series of amino acids, nucleosides, and deoxynucleosides were identified. In the fingerprint assessments, principal component analysis and Hotelling T2 analysis yielded the best results. The results generally indicated that there was a significant difference among products of batch-to-batch or from different manufacturers. Abnormal samples and its discriminatory components were also explored. In summary, the established fingerprinting method with multivariate statistical analysis could offer an efficient, reliable, and practical approach for quality consistency evaluation of transfer factor injection, providing a reference for the quality control of other multicomponent biochemical drugs.

Afferent determination of transfer factor formation in the rat spinal cord

The mechanisms causing the appearance of transfer factor (TF) in the cerebrospinal tissue of rats were studied. Intracerebral TF injections to intact recipients were found to change asymmetrically the reflectory muscular responses. TF could be found in the extract of the rat spinal cord in rats with cut off n. tibialis sin. or with alcohol-novocaine blockade of posterior left tibial muscles, i.e., the reaction of the cerebral cells to the break in axon integrity is not responsible for TF formation. The appearance of TF in the cerebrospinal tissue less than two hours after alcohol-novocaine muscular blockade does not suggest that the axon integrity is the cause initiating TF formation. It is assumed that the deafferentation determines TF appearance in the cerebrospinal tissue.

Adoptive Transfer of Delayed Hypersensitivity and Protective Immunity to Eimeria tenella with Chicken-Derived Transfer Factor

Delayed hypersensitivity (DH) and protective immunity were transferred to nonimmune 4- and 10-week-old broiler chickens with transfer factor (TF) prepared from splenic leukocytes of chickens immunized with CocciVac® D. Only chickens injected with the immune TF showed DH by wattle reaction to oocyst antigen and protective immunity to Eimeria tenella challenge infection. Chickens given a single injection of TF 5 days before challenge infection exhibited a significant (P<.05) DH response at the time of infection. Immune TF preparations were active at concentrations of 100, 200, or 400 mg. Neither DH nor protective immunity was transferred to chickens injected with the TF-diluent control or nonimmune TF. The nonimmune TF was prepared from chickens kept free of coccidial infection. These findings indicated that TF prophylaxis produced beneficial results in nonimmune chickens by conferring some protection against challenge with E. tenella. The effects of TF on T-lymphocyte mediated protective immunity to coccidia in chickens are discussed.

Immunotherapy in Leprosy-Reply

In Reply.— We appreciate Dr Fusaro's discussion of research on the use of transfer factor in efforts to enhance the immunity of lepromatous patients. Our article cited the work of Hastings and Job, 1 who treated four lepromatous patients and one borderline patient with transfer factor obtained from approximately 7.4×10 9 lymphocytes given in 36 divided doses during 12 weeks. Clinical reversal reactions (immunologic upgrading) were observed in the four lepromatous patients but not in the borderline patient. 2 Histopathologically, skin biopsy specimens of the four lepromatous patients showed a reduction of acid-fast bacilli and proliferation of epithelioid and giant cells. In one lepromatous patient, the reversal reaction persisted 14 months after the injections were stopped. In two lepromatous patients, they continued to appear four to 28 months after the last transfer factor injection was given. In the remaining lepromatous patient, the reversal reaction continued five months after the last injection,

Acquired Cytomegalovirus Infection in an Infant—Serum Interferon Activity after Transfer Factor Injection—

Acquired Cytomegalovirus Infection in an Infant—Serum Interferon Activity after Transfer Factor Injection—

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.

Immunotherapy of Leprosy (2nd report)

Four cases with leprosy were treated with immunotherapy by means of injection of transfer factor (TF). In the first case, BI reached the level of 1 in 1975, which thereafter continued for three years despite of continuation of chemotherapy. And this case was treated with the transfusion of leucocytes. The immunotherapy by means of injection of TF started nine weeks after the termination of transfusion of leucocytes. Also in the next case, the number of leprosy bacilli decreased to a small number by chemotherapy, but could not reach the negetivity despite of continuation of chemotherapy. In the other two cases, the injection of TF started at the stadium in which the number of leprosy bacilli decreased to middle grade by chemotherapy. The type of eprosy was BL in three cases, and LL/BL in a case.TF was extracted from the leucocytes of normal healthy adults. One vial of TF was injected once or twice weekly, or two vials of TF were injected once weekly. The total number of times of injection of TF is 25 in the first case, and 31 in the 2 nd case. And the total amount of TF is 38 vials in the first case, and 45 vials in the 2 nd case. In the other 2 cases, the number of times was 16 and 13 respectively, and the total amount was 16 vials and 13 vials respectively.The reversal reaction did not occur in every cases. The tendency of decrease of number of leprosy bacilli was somewhat observed in the first 2 cases, but not observed in the other 2 cases. In a case of first two cases, the number of T-cell increased a little.The function of lymphocytes did not change by the injection of TF. The lepromin reaction of first two cases was examined. In a case, the marked but temporarily positive Fernandez reaction occurred, and the Mitsuda reaction changed from negative to doubtful reation. But despite of the injection of TF made many times, clearly positive Mitsuda reaction did not occur. The amount of immunoglobulin and complement did notchange.Judging from the data obtained from this study, big hope cannot be placed on TF.

Transfer of delayed cutaneous hypersensitivity with transfer factor

The effect of dialyzable transfer factor from 16 donors on transfer of delayed skin reactivity was studied in 20 patients with cellular immunodeficiency syndromes. Successful transfer of delayed hypersensitivity was achieved in 50 of the 89 opportunities. There were three additional instances in which recipients became reactive to antigens to which the donors were unresponsive. Four patients received multiple injections of transfer factor from donors who were unresponsive to candida; in no instance did a recipient become reactive to candida, although three became reactive to other donor-responsive antigens. The data also showed that conversions of skin responses by recipients occurred as independent events and not in all-or-none manner. The results of this investigation are interpreted as being compatible with antigen-specific activities in dialyzable transfer factor.

Transfer factor therapy in a case of pemphigus vegetans associated with chronic mucocutaneous candidiasis

A 19-year-old white male with both pemphigus vegetans and chronic mucocutaneous candidiasis was treated with transfer factor (TF) based on possible common pathophysiologic relationships between these disorders and immune abnormalities. He was incompletely responsive to treatment with prednisolone, methotrexate, and topical micronazole. During 77 weeks of TF therapy, the patient showed gradual but continuous improvement of both diseases characterized by periods of complete remission and occasional mild exacerbations. Administration of other drugs was not necessary. When TF was withheld both diseases flared but regressed after reinstituting TF injections. Thus, TF may be therapeutically beneficial in some patients with the milder forms of pemphigus, and a relationship between cellular immune abnormalities correctable by TF and pemphigus is suggested.

Human transfer factor in vitro: identification of L-serine and glycine as components with augmenting effect in lymphocyte transformation assay.

The components of human leucocyte dialysate thought to contain transfer factor, which irresponsible for its capacity to augment antigen or mitogen induced lymphocyte blasogenesis in vitro, were determined by comparing the activity of the original dialysate with its fractions derived from chromatography on Sephadex G‐10. Augmentation of leucoagglutinin (LA) induced transformation was only observed using the original dialysate and two fractions (IIb and IIc) eluting before the total volume of the column. These fractions contained the majority of free amino acids in the dialysate, and no trichloroacetic acid (TCA) precipitable material. Synthetic mixtures, containing the same amount of free amino acids as the fractions, augmented both tuberculin PPD and LA induced blastogenesis in a similar manner to the fractions. The augmenting activity of the synthetic mixture and hence, presumably, the dialysate fractions seemed to be due mostly to l‐serine and glycine, non‐essential amino acids not present in MEM‐S, the culture medium used. No augmenting affect by leucocyte dialysate was seen when MEM‐S was replaced by RPMI 1640, a culture medium containing both l‐serine and glycine. The results suggest that the non‐specific in vitro activity of leucocyte dialysate in this test may be due to a medium supplementation effect and that this phenomenon is probably not relevant to the nonspecific consequences of injection of transfer factor in vivo.

Effect of Transfer Factor and Zoster Immunoglobulin in Patients with Varicella-Zoster Infection and Malignancy

Immunotherapy was given to 13 patients suffering from lymphoproliferative diseases complicated by varicella-zoster (VZ) infection. Five patients received transfer factor (TF) only, 6 received TF and zoster immunoglobulin (ZIG), and 2 received ZIG only. ZIG did not seem to alter the course of the infection. Cessation of vesicle formation and initiation of crust formation took place within 1 day after the first injection of TF in 5 patients with a localized zoster. In 4 patients suffering from an early dissemination of VZ infection, cessation of vesicle formation took place within 1 day (1 patient), 2 days (1 patient), 3 days (1 patient) or 4 days (1 patient) after the first injection of TF. An increase in serum interferon was observed in 4 of 9 patients who received TF, while no increase in serum interferon was observed in the control groups. Administration of a high-titer ZIG preparation did not seem to depress the humoral antibody response when combined with TF therapy. Therapy with TF in combination with ZIG seemed to have a beneficial effect in patients with malignancy when administered early in the acute VZ infection.

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.

Treatment of Bechçet's Syndrome With Transfer Factor

Six patients with Behçet's syndrome were treated with transfer factor (TF) from randomly selected donors. Mucocutaneous symptoms and signs were predominant at the time that TF injections were started. Three patients showed great improvement, one moderate improvement, and one was unresponsive to multiple injections of TF from different donors. One case was uninterpretable because of concomitant administration of high doses of prednisone and chlorambucil and brief treatment with TF. These results indicate that TF therapy may be beneficial in some patients with Behçet's syndrome and that a trial of TF is warranted at least in the absence of severe ocular or neurologic manifestations.

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...

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.

Transfer Factor Treatment of Patients with Multiple Sclerosis

In five patients with definite multiple sclerosis and lack of cell‐mediated immunity to measles and parainfluenza virus antigens, various immunological parameter were studied before and during transfer factor treatment. The study showed that cell‐mediated immunity to measles virus antigen, as evaluated by the leukocyte migration agarose test, could temporarily be restored, using repeated injections of transfer factor pooled from unselected, normal blood donors.

Treatment of Chronic Muco‐cutaneous Candidiasis by Lymphocyte Transfer Factor

A beneficial clinical effect from the administration of lymphocyte transfer factor is described in six patients with idiopathic early onset chronic muco-cutaneous candidiasis. Five patients in two families showed a familial disease pattern. Dermal anergy and failure to produce migratory inhibition factor with intact general immune function were found in patients tested. Antifungal chemotherapy was effective in clearing or markedly reducing the candidiasis and remission was maintained by repeated injections of transfer factor. Therapy was monitored using Candida skin test.

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.

The principle of immunopotentiation in treatment of rheumatoid arthritis: effect of transfer factor.

Three patients (aged 3 to 7 years) suffering from active juvenile rheumatoid arthritis, with pronounced general illness, synovitis in multiple joints, and, two of them, typical fluctuating high fever, were treated with dialyzable transfer factor. During the treatment period, varying from 3 to 5 months, the patients received from 5 to 10 injections of transfer factor, each dose corresponding to the biological material obtained from 400 to 450 ml of normal blood. There was a marked improvement of the general condition, most pronounced in the two patients with the most severe disease, in whom the temperature was normalized. Joint functions also improved. There were changes in cell‐mediated immunity, with conversion of previously negative responses to antigens in delayed hypersensitivity in vivo and lymphocyte transformation in vitro. Lymphocyte transformation with unspecific mitogens and allogeneic lymphocytes, the proportions in peripheral blood of B and T lymphocytes, as well as Fc receptor‐bearing lymphocytes were normal and remained so during the observation period.

A new principle of immunotherapy in rheumatoid arthritis: treatment with transfer factor.

Three patients with severe affectioAs of juvenile rheumatoid arthritis were treated with 5-10 injections of transfer factor for 3–5 months. The results with this new principle of immunotherapy in rheumatoid arthritis are promising and can be summarized as follows: (1) The therapy has not in any case resulted in any flare-up of the disease. (2) There has been no clinical progression of the disease and none of the laboratory parameters, including X-ray findings and immunologic studfes, have indicated any further development of the disease during the therapeutic period. (3) There has been a definite improvement in the general condition including normalizing of the temperature, less morning stiffness and pain, improved ability for general activity and participation in physical treatment. (4) In two cases there was also an improvement of the joint function. Changes in cell-mediated immunity occurred during the treatment, as evidenced by conversion of previously negative antigen responses by in vitro and in vivo testing.