Transfer Factor: antipathogenic and antiinflammatory effects

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Presse Med. 1984 Mar 3;13(9):537-40.

[Treatment of herpes infections with transfer factor]

[Article in French] Rosenfeld F, Viza D, J, Vich JM,

Binet O, Aron-Brunetire R.

Twelve patients suffering from recurrent herpetic infections

resistant to several current therapies were treated for a 3 to 10 months

period with a bovine transfer factor specific to Herpes simplex virus of

type 1 and 2. The results obtained showed that this treatment was

capable of dramatically reducing the intensity, duration and frequency

of the relapses. This preliminary clinical trial suggests that specific

transfer factor administered orally could be an effective treatment of

herpes infections.

Publication Types: * Clinical Trial * English Abstract

* Research Support, Non-U.S. Gov't

PMID: 6230646 [PubMed - indexed for MEDLINE]

Lancet. 1981 Jul 18;2(8238):122-4.

Treatment of childhood combined Epstein-Barr virus/cytomegalovirus

infection with oral bovine transfer factor.

JF, Minnich LL, Jeter WS, Pritchett RF, Fulginiti VA, Wedgwood

RJ.

An illness lasting for two years, with recurrent fever, rash,

abdominal pain, and arthralgia, developed in a four year old boy. He was

found to have a combined Epstein-Barr virus and cytomegalovirus (CMV)

infection. His symptoms, CMV in his urine, and an absent in vitro

lymphocyte response to CMV antigen persisted for two years. After

treatment with orally administered bovine transfer factor clinical

symptoms and viruria disappeared and specific immunity to CMV developed.

Evaluation of this treatment in chronic virus infections is warranted.

Publication Types: * Case Reports * Research Support,

Non-U.S. Gov't * Research Support, U.S. Gov't, P.H.S.

PMID: 6113484 [PubMed - indexed for MEDLINE]

Immunopharmacol Immunotoxicol. 2006;28(3):471-83.

In vitro antibacterial activity of bovine dialyzable leukocyte extract.

Armides Franco-Molina M, Mendoza-Gamboa E, Castillo-Tello P,

Tamez-Guerra RS, Villarreal-Trevi–o L, Tijerina-Menchaca R,

Castillo-Le—n L, Zapata-Benavides P, Rodr'guez-Padilla C.

Departamento de Microbiolog'a e Inmunolog'a, Laboratorio de

Inmunolog'a y Virolog'a, Facultad de Ciencias Biol—gicas,

Universidad Aut—noma de Nuevo Le—n, Nuevo Le—n, MŽxico.

The rapidly developing resistance of many infectious pathogenic

organisms to modern drugs has spurred scientists to search for new

sources of antibacterial compounds. One potential candidate, bDLE

(dialysis at 10 to 12 kDa cut-off) and its fractions ( " S " and " L " by 3.5

kDa cut-off and I, II, III, and IV by molecular exclusion

chromatography), was evaluated for antibacterial activity against

pathogenic bacterial strains (Staphylococcus aureus, Streptococcus

pyogenes, Lysteria monocytogenes, Escherichia coli, Pseudomonas

aeruginosa, and Salmonella typhi) using standard antimicrobial assays. A

minimum inhibitory concentration (MIC) of bDLE and its fractions was

determined by agar and broth dilutions methods. Only bDLE and its " S "

fraction had an effect upon all bacteria evaluated (MIC ranging from

0.29 to 0.62 U/ml), and the bactericidal and bacteriostatic effects

(evaluated by MTT assay) were bacterial species-dependent. These results

showed a remarkable in vitro antibacterial property of bDLE against

several pathogenic bacteria.

Publication Types: * Research Support, Non-U.S. Gov't

PMID: 16997795 [PubMed - indexed for MEDLINE]

3: Int Immunopharmacol. 2004 Dec 15;4(13):1577-86.

Bovine dialyzable leukocyte extract protects against LPS-induced, murine

endotoxic shock.

Franco-Molina MA, Mendoza-Gamboa E, Castillo-Le—n L,

Tamez-Guerra RS, Rodr'guez-Padilla C. Laboratorio de

Inmunolog'a y Virolog'a, Departamento de Microbiolog'a e

Inmunolog'a, Facultad de Ciencias Biol—gicas, Universidad

Aut—noma de Nuevo Le—n, Apartado Postal 46 F, San Nicol‡s de

los Garza, N.L., MŽxico.

The pathophysiology of endotoxic shock is characterized by the

activation of multiple pro-inflammatory genes and their products which

initiate the inflammatory process. Endotoxic shock is a serious

condition with high mortality. Bovine dialyzable leukocyte extract

(bDLE) is a dialyzate of a heterogeneous mixture of low molecular weight

substances released from disintegrated leukocytes of the blood or

lymphoid tissue obtained from homogenized bovine spleen. bDLE is

clinically effective for a broad spectrum of diseases. To determine

whether bDLE improves survival and modulates the expression of

pro-inflammatory cytokine genes in LPS-induced, murine endotoxic shock,

Balb/C mice were treated with bDLE (1 U) after pretreatment with LPS (17

mg/kg). The bDLE improved survival (90%), suppressed IL-10 and IL-6, and

decreased IL-1beta, TNF-alpha, and IL-12p40 mRNA expression; and

decreased the production of IL-10 (P<0.01), TNF-alpha (P<0.01), and IL-6

(P<0.01) in LPS-induced, murine endotoxic shock. Our results demonstrate

that bDLE leads to improved survival in LPS-induced endotoxic shock in

mice, modulating the pro-inflammatory cytokine gene expression,

suggesting that bDLE is an effective therapeutic agent for inflammatory

illnesses associated with an unbalanced expression of pro-inflammatory

cytokine genes such as in endotoxic shock, rheumatic arthritis and other

diseases.

Publication Types: * Research Support, Non-U.S. Gov't

PMID: 15454111 [PubMed - indexed for MEDLINE]

Cytotherapy. 2007;9(4):379-85.

Bovine dialyzable leukocyte extract modulates cytokines and nitric oxide

production in lipopolysaccharide-stimulated human blood cells.

Franco-Molina MA, Mendoza-Gamboa E, Castillo-Tello P, Isaza-Brando

CE, Garc'a ME, Castillo-Le—n L, Tamez-Guerra RS,

Rodr'guez-Padilla C. Departamento de Inmunolog'a y

Virolog'a, Universidad Aut—noma de Nuevo Le—n, San

Nicol‡s de los Garza, Nuevo Le—n, MŽxico.

BACKGROUND: In the current study, we determined whether bovine

dialyzable leukocyte extract (bDLE) modulates lipopolysaccharide

(LPS)-induced nitric oxide and cytokine overproduction. METHODS: Human

whole blood cells were treated with LPS (50 ng) + bDLE (1 U). RESULTS:

The bDLE treatment decreased nitric oxide as well as TNF-alpha, IL-6 and

IL-10 (P <0.01) cytokine production. In addition, it decreased

TNF-alpha, IL-1beta and IL-6 mRNA expression and suppressed IL-10 and

IL-12p40 mRNA expression, but did not modulate IL-8 mRNA expression in

LPS-stimulated human blood cells. DISCUSSION: Our results suggest that

bDLE may effectively modulate the fatal symptoms of hypotensive shock

associated with endotoxin (LPS)-induced nitric oxide and cytokine

production, and this may offer therapeutic potential for the treatment

of endotoxic shock.

Publication Types: * Research Support, Non.S. Gov't

PMID: 17573613 [PubMed - indexed for MEDLINE]

Biotherapy. 1996;9(1-3):67-72.

Orally administered HSV-specific transfer factor (TF) prevents

genital or labial herpes relapses.

Pizza G, Viza D, De Vinci C, Palareti A, Cuzzocrea D, Fornarola V,

Baricordi R. Immunodiagnosis and Immunotherapy Unit, 1st-Division of

Urology, S. Orsola-Malpighi Hospital, Bologna, Italy.

Forty-four patients suffering from genital (22) and labial (22)

herpes were orally treated with HSV-1/2-specific transfer factor (TF).

TF was obtained by in vitro replication of a HSV-1/2-specific bovine

dialysable lymphocyte extract. Treatment was administered bi-weekly the

first 2 weeks, and then weekly for 6 months, most patients received 2-3

courses. The total observation period for all patients before treatment

was 26,660 days, with 544 relapses, and a relapse index of 61.2, whereas

the cumulative observation period during and after treatment was 16,945

days, with a total of 121 relapsing episodes and a cumulative RI of 21.4

(P < 0.0001). Results were equally significant when the 2 groups of

patients (labial and genital) were considered separately. These

observations confirm previous results obtained with bovine HSV-specific

TF, and warrant further studies to establish HSV-specific TF as a choice

of treatment for preventing herpes recurrences.

Publication Types: * Research Support, Non-U.S. Gov't

PMID: 8993760 [PubMed - indexed for MEDLINE]

5: Biotherapy. 1996;9(1-3):61-6.

Efficacy of transfer factor in treating patients with recurrent

ocular herpes infections.

Meduri R, Campos E, Scorolli L, De Vinci C, Pizza G, Viza D. Eye

Physiopathology Clinical Service, University of Bologna, Italy.

Recurrent ocular herpes is an insoluble problem for the clinician.

As cellular immunity plays an important role in controlling herpes

relapses, and other studies have shown the efficacy of HSV-specific

transfer factor (TF) for the treatment of herpes patients, an open

clinical trial was undertaken in 134 patients (71 keratitis, 29

kerato-uveitis, 34 uveitis) suffering from recurrent ocular herpetic

infections. The mean duration of the treatment was 358 days, and the

entire follow-up period 189,121 before, and 64,062 days after TF

treatment. The cell-mediated immune response to the viral antigens,

evaluated by the lymphocyte stimulation test (LST) and the leucocyte

migration test (LMT) (P < 0.001), was significantly increased by the TF

treatment. The total number of relapses was decreased significantly

during/after TF treatment, dropping from 832 before, to 89 after

treatment, whereas the cumulative relapse index (RI) dropped, during the

same period, from 13.2 to 4.17 (P < 0.0001). No side effects were

observed. It is concluded that patients with relapsing ocular herpes can

benefit from treatment with HSV-specific TF.

Publication Types: * Clinical Trial

PMID: 8993759 [PubMed - indexed for MEDLINE]

6: J Infect Dis. 1990 Jan;161(1):108-12.

A controlled trial of bovine dialyzable leukocyte extract for

cryptosporidiosis in patients with AIDS.

McMeeking A, Borkowsky W, Klesius PH, Bonk S, Holzman RS, Lawrence

HS. Department of Medicine, New York University Medical Center, NY

10016.

Cryptosporidial infection causes severe diarrheal disease in

patients with AIDS. Fourteen patients with AIDS and symptomatic

cryptosporidiosis were treated with a specific bovine dialyzable

leukocyte extract (immune DLE) prepared from lymph node lymphocytes of

calves immunized with cryptosporidia or a nonspecific (nonimmune) DLE

prepared from nonimmunized calves. Six of 7 patients given immune DLE

gained weight and had a decrease in bowel movement frequency, with

eradication of oocysts from stool in 5 patients. Six of 7 patients given

nonimmune DLE showed no decrease in bowel movement and 4, no clearing of

oocytes from stool; 5 continued to lose weight. Subsequently, 5 of these

7 were treated with immune DLE; 4 had a decrease in bowel movement

frequency and significant weight gain, with eradication of oocytes from

stool in 2 patients. Immune DLE produces sustained symptomatic

improvement in patients with AIDS and active cryptosporidiosis, but lack

of an appropriate cryptosporidial antigen allows only postulation that

an augmentation of cellular immunity to Cryptosporidium parvum induced

by immune DLE resulted in the microbiologic and clinical improvement

observed.

Publication Types: * Clinical Trial * Controlled

Clinical Trial * Randomized Controlled Trial * Research

Support, U.S. Gov't, P.H.S.

PMID: 2404072 [PubMed - indexed for MEDLINE]

7: Acta Virol. 1988 Jan;32(1):6-18.

De novo initiation of specific cell-mediated immune responsiveness

in chickens by transfer factor (specific immunity inducer) obtained from

bovine colostrum and milk.

GB, Poindexter C, Fort JD, Ludden KD. Amtron, Inc.,

ton, South Carolina.

Transfer factors (TF) were prepared from colostrum and milk of

bovines previously immunized with antigens obtained from Coccidioides

immitis, infectious bovine rhinotracheitis virus, or from the viral

agents responsible for avian Newcastle disease, laryngotracheitis

disease or infectious bursal disease. The ability of bovine TF to

transfer specific cell-mediated immune responsiveness to a markedly

xenogenic species was studied using specific pathogen free (SPF) and

standard commercial (SC) chickens as model recipients. Cell-mediated

immune responsiveness was documented using one or more of the following

for each antigen (organism) studied: (a) an in vitro chicken leukocyte

(heterophil) migration inhibition assay; ( delayed-wattle reactivity;

or © protection from clinical disease. Chicken TFs obtained from

spleens of immune donors were evaluated in parallel to bovine TF's in

selected comparative studies. Bovine TF also referred to as specific

immunity inducer (SII), and chicken TF were found to initiate

antigen-specific cell-mediated immunity de novo in previously non-immune

SPF chickens as well as in SC chickens despite the presence of

maternally acquired humoral antibody which may serve as a " barrier " to

immunization of SC chickens when commercially available vaccines are

administered by parenteral routes. Bovine TF's specific for

laryngotracheitis virus or infectious bursal disease virus afforded

protection equal to that found for commercially available vaccines.

Bovine TF's action was rapid (less than a day) and of relatively long

duration at least 35 days.

PMID: 2897772 [PubMed - indexed for MEDLINE]

8: Clin Immunol Immunopathol. 1987 Sep;44(3):329-34.

Treatment of cryptosporidiosis with oral bovine transfer factor.

Louie E, Borkowsky W, Klesius PH, Haynes TB, Gordon S, Bonk S,

Lawrence HS.

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 alpha-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.

PMID: 3621678 [PubMed - indexed for MEDLINE]

9: Cell Immunol. 1986 Jul;100(2):555-62.

Specific transfer factor protects mice against lethal challenge with

herpes simplex virus.

Viza D, Vich JM, J, Rosenfeld F, Davies DA.

Bovine transfer factor (TFd) specific to herpes simplex virus (HSV)1

or to HSV2 was prepared by immunizing calves with the corresponding

virus. The TFd preparations were then injected into Swiss mice in an

attempt to protect them against a subsequent lethal challenge with HSV1

or HSV2 virus. It was thus shown that injection of anti-HSV TFd protects

the mice against the corresponding HSV virus, whereas the injection of a

nonspecific TFd (anti-CMV) fails to protect against a challenge with

HSV1. Furthermore, a dose-response effect was observed, since potent TFd

preparations were ineffective when they were used at one-fifth of the

original concentration. It seems, therefore, that animal models may be

used to assay the potency of TFd preparations specific for herpes

viruses.

Publication Types: * Research Support, Non-U.S. Gov't

PMID: 3019568 [PubMed - indexed for MEDLINE]